Multiple Myeloma – Treatments, Economic Burden, And End Of Life Care

This dissertation aimed at filling the gaps in the body of multiple myeloma (MM) literature by comparing overall survival and safety of first line maintenance or continuous treatment, and assessing disease lifetime costs, phase-specific costs and its drivers among elderly newly diagnosed (NDMM) patients. Moreover, it aimed to assess trends in EOL care and the impact of PCC on EOL care outcomes among elderly MM patients. First, this study assessed the comparative safety and effectiveness among those who received first line LEN-based treatment versus those who received first line BORT-based treatment. The results from the study demonstrates an overall survival benefit and similar toxicity risk for patients receiving first line LEN-based continuous or maintenance treatment over those who received first line BORT-based treatment. Further, the study results highlighted the substantial economic burden associated with MM care, in spite of the disease having low prevalence as compared to some of the other cancers. The incremental phase-specific costs were highest for the initial care phase, folloby the terminal phase, with costs being slightly lower for the continuing care phase, and lowest for the pre-diagnosis phase. Inpatient and outpatient costs were the major drivers of costs in all the four phases. Pharmacy costs were a significant driver of costs in the initial and terminal phases, and were the biggest cost driver in the continuing care phase. Last, it assessed trends in aggressiveness of EOL care outcomes over time. While certain indicators of aggressive EOL care remained stable over time, we observed an increasing trend for multiple ED visits and ICU stays. Moreover, this study assessed the impact of palliative care consultations on receiving aggressive EOL care, and healthcare resource use and costs at EOL. Results indicate that early palliative care consultations have the potential to reduce aggressive EOL care, and curtail healthcare resource use and costs at EOL. Study findings about clinical and economic outcomes will help inform clinicians’ treatment decisions, aid policy discussions regarding MM care and coverage, and help design interventions to integrate early palliative care into routine care among elderly MM patients

Burden Of Depression Among Individuals With Irritable Bowel Syndrome(IBS) In The Medicaid Population

Objective: to determine the period prevalence of IBS and comorbid depression among individuals with Irritable Bowel Syndrome (IBS) in multi-state Medicaid population, and to assess the impact of comorbid depression on healthcare utilization and costs among individuals with IBS enrolled in fee-for-service Medicaid program. Methods: a retrospective cohort study was conducted using 2006-2008 Medicaid analytic extract files for 39 states. Beneficiaries with IBS were identified based on any medical claims for the disease. Beneficiaries with one or more medical claims for depression during the study period were considered to have had comorbid depression. For each beneficiary, the first claim for IBS in 2007 was considered as the index date. 12-month post index date all-cause and IBS-related healthcare utilization and costs were computed for each of the four medical service components “inpatient, outpatient, emergency room, and prescription drug. Generalized linear models were used to assess the impact of comorbid depression on healthcare utilization and costs. Results: the period prevalence of IBS in the population was 4.4 per 1,000 Medicaid beneficiaries. The period prevalence of comorbid depression among beneficiaries with IBS was 26.88%. Beneficiaries with IBS and depression had significantly greater all-cause and IBS-related inpatient, IBS-related outpatient, all-cause emergency room, all-cause and IBS-related prescription drug utilization, and IBS-related outpatient, all-cause and IBS-related emergency room, and all-cause and IBS-related prescription drug costs as compared to those without depression. Conclusion: given the impact on healthcare use and costs, there is a need for better screening and management of depression in this population

Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency

PURPOSE: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a life-threatening, ultrarare inborn error of metabolism. Case reports described successful D,L-3-hydroxybutyrate (D,L-3-HB) treatment in severely affected MADD patients, but systematic data on efficacy and safety is lacking.METHODS: A systematic literature review and an international, retrospective cohort study on clinical presentation, D,L-3-HB treatment method, and outcome in MADD(-like) patients.RESULTS: Our study summarizes 23 MADD(-like) patients, including 14 new cases. Median age at clinical onset was two months (interquartile range [IQR]: 8 months). Median age at starting D,L-3-HB was seven months (IQR: 4.5 years). D,L-3-HB doses ranged between 100 and 2600 mg/kg/day. Clinical improvement was reported in 16 patients (70%) for cardiomyopathy, leukodystrophy, liver symptoms, muscle symptoms, and/or respiratory failure. D,L-3-HB appeared not effective for neuropathy. Survival appeared longer upon D,L-3-HB compared with historical controls. Median time until first clinical improvement was one month, and ranged up to six months. Reported side effects included abdominal pain, constipation, dehydration, diarrhea, and vomiting/nausea. Median D,L-3-HB treatment duration was two years (IQR: 6 years). D,L-3-HB treatment was discontinued in 12 patients (52%).CONCLUSION: The strength of the current study is the international pooling of data demonstrating that D,L-3-HB treatment can be effective and safe in MADD(-like) patients.</p

Minimal clinically important difference for the 6-min walk test : literature review and application to Morquio A syndrome

Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multisystemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distributionbased methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy. The literature review showed a mean MCID for the 6MWT of 7% change (range 3–15%) in studies using anchor-based methods and a 9% change (range 4–16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population

Additional file 2: of Minimal clinically important difference for the 6-min walk test: literature review and application to Morquio A syndrome

Percent change from MOR-004 baseline in 6-min walk test (6MWT) distance at 2 years in the MOR-005 Modified Per-Protocol (MPP) population (excluding patients who had orthopedic surgery during the extension study or missed ≥20% of their scheduled elosulfase alfa infusions) and comparable, untreated patients from the MorCAP natural history study. (DOCX 12 kb

Dietary Management of the Ketogenic Glycogen Storage Diseases

The glycogen storage diseases (GSDs) comprise a group of rare inherited disorders of glycogen metabolism. The hepatic glycogenolytic forms of these disorders are typically associated with hypoglycemia and hepatomegaly. For GSD I, secondary metabolic disturbances include fasting hyperlactatemia, hyperuricemia, and hyperlipidemia. Glycogen storage disease III is caused by reduced activity of the debrancher enzyme, GSD VI by phosphorylase, and GSD IX by phosphorylase kinase. It has often been reported that the non-GSD I group of disorders have a benign course. However, myopathy, cardiomyopathy, and cirrhosis have been reported significant clinical morbidities associated with GSD III and IX in particular. There have been a range of reports indicating high-protein diets, high-fat diets, medium chain triglyceride (MCT), modified Atkins diet, and therapeutic ketones as rescuing severe phenotypes of GSD III in particular. The etiology of these severe phenotypes has not been defined. Cases presented in this report indicate potential harm from excessive simple sugar use in GSD IX C. Review of the literature indicates that most interventions have reduced the glycemic load and provide alternate substrates for energy in rescue situations. Prevention of complications is most likely to occur with a mixed balanced low glycemic index diet potentially with relative increases in protein

Size engineered Cu-doped alpha-MnO2 nanoparticles for exaggerated photocatalytic activity and energy storage application

This investigation involves the synthesis of Cu doped alpha-MnO2 nanoparticles through modified Chemical route. Obtained nanoparticles (diameter_(similar to)5 nm to (similar to)18 nm) are found mostly stable at high temperature and its size can be modulated by Cu doping and post sintering temperature variation. Cyclic voltammetry and galvanostatic charge-discharge performance indicate the excellent cycling stability along with a maximum capacitance of 229.5 F/g for current density of 1 A/g. Our fabricated device is also capable to power up 73 numbers of LED for 10 min after being charged for 10 s. From the photocatalytic experiment, degradation efficiency of 73.1% has been achieved by using even ultra diluted aqueous solution (0.0025 g/L) of active material to degrade the pollutant dye like Brilliant Green of 5 ppm concentration. Entire results suggest that the synthesized materials are the promising candidate to be used in photocatalysis and supercapacitive application purpose