Microbial cell factories for the sustainable manufacturing of B vitamins.

Vitamins are essential compounds in human and animal diets. Their demand is increasing globally in food, feed, cosmetics, chemical and pharmaceutical industries. Most current production methods are unsustainable because they use non-renewable sources and often generate hazardous waste. Many microorganisms produce vitamins naturally, but their corresponding metabolic pathways are tightly regulated since vitamins are needed only in catalytic amounts. Metabolic engineering is accelerating the development of microbial cell factories for vitamins that could compete with chemical methods that have been optimized over decades, but scientific hurdles remain. Additional technological and regulatory issues need to be overcome for innovative bioprocesses to reach the market. Here, we review the current state of development and challenges for fermentative processes for the B vitamin group.

Cost minimization comparison of oral UFT/leucovorin versus 5-fluorouracil/leucovorin as adjuvant therapy for colorectal cancer in Taiwan.

AIM: Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective. PATIENTS & METHODS: The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome. RESULT: A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV. CONCLUSION: UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.

Vitamins for Cardiovascular Diseases: Is the Expense Justified?

Despite the knowledge that a well-balanced diet provides most of the nutritional requirements, the use of supplemental vitamins is widespread among adults in the United States. Evidence from large randomized controlled trials over the last 2 decades does not support vitamin supplementation for the reduction of cardiovascular risk factors or clinical outcomes. Many of the vitamins used in common practice likely are safe when consumed in small doses, but long-term consumption of megadoses is not only expensive but has the potential to cause adverse effects. Therefore, a need exists to revisit this issue, reminding the public and healthcare providers about the data supporting the use of vitamins for cardiovascular disease, and the potential for harm and the expense associated with their unnecessary use. In this review, we highlight the scientific evidence from randomized controlled studies regarding the efficacy and safety of vitamin supplementation for primary and secondary prevention of cardiovascular diseases and outcomes. We also draw attention to issues related to widespread and indiscriminate use of vitamin supplements and the need to educate the public to curtail unnecessary consumption and expense by limiting their use based on strong scientific evidence.

Case Report: Diabetic Foot Ulcer Infection Treated with Topical Compounded Medications.

An adult diabetic male with three toes amputated on his right foot presented with an ulcer infection on his left foot, unresponsive to conventional antifungal oral medication for over two months. The ulcerated foot wound had a large impairment on the patient's quality of life, as determined by the Wound-QoL questionnaire. The compounding pharmacist recommended and the physician prescribed two topical compounded medicines, which were applied twice a day, free of charge at the compounding pharmacy. The foot ulcer infection was completely resolved following 13 days of treatment, with no longer any impairment on the patient's quality of life. This scientific case study highlights the value of pharmaceutical compounding in current therapeutics, the importance of the triad relationship, and the key role of the compounding pharmacist in diabetes care.

Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors.

OBJECTIVE: The aim of this study was to estimate the cost-savings attainable if all patients aged ≥65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health. SETTING: Primary care setting in Alberta, Canada. PARTICIPANTS: Seniors of age 65 years and older currently receiving intramuscular vitamin B12 therapy. INTERVENTION: Oral vitamin B12 therapy at 1000 µg/day versus intramuscular therapy at 1000 µg/month. PRIMARY AND SECONDARY OUTCOME MEASURES: Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees. RESULTS: Over 5 years, if all Albertans aged 65 years and older who currently receive intramuscular B12 are switched to oral therapy, our model found that $C13 975 883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8 444 346 could be saved from reduced administration costs alone. CONCLUSIONS: Oral B12 therapy has been shown to be an effective therapeutic option for patients with vitamin B12 deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12 therapy as a clinically and cost-effective first-line therapy for vitamin B12 deficiency.

Vitamin B12 intramuscular injections versus oral supplements: a budget impact analysis.

BACKGROUND: Vitamin B12 deficiency can lead to adverse health effects such as anemia and, in some cases, permanent neurologic damage. In Canada, patients with vitamin B12 deficiency are typically given intramuscular injections, which incur considerable cost and inconvenience. The clinical evidence-based analysis has found that oral supplementation is as effective as intramuscular injections. OBJECTIVES: This economic analysis aimed to estimate the cost savings of switching from intramuscular injections to high-dose oral supplements for patients aged 18 years and older with confirmed vitamin B12 deficiency. DATA SOURCES: Population-based administrative databases for Ontario were used to identify patients receiving vitamin B12 intramuscular injections in any fiscal year between 2006 and 2011. The Ontario Drug Benefit (ODB) database was used to identify patients who were prescribed vitamin B12 injections, and the Ontario Health Insurance Plan database was used to identify all physician claims for intramuscular injections as well as laboratory tests assessing vitamin B12 levels. The Registered Physicians Database was used to identify the type of physician; the analysis was restricted to family physicians and internists. REVIEW METHODS: Two cohorts of patients were identified. For cohort 1, the ODB database was used to identify patients who were prescribed vitamin B12 injections. Those covered under the ODB are 65 years of age or older and are economically deprived. A second cohort was created to capture those 18 to 64 years of age receiving injections. Cohort 2 consisted of patients (not in cohort 1) who received 6 or more intramuscular injections within 1 year and had a laboratory test 2 months before the intramuscular injection claim. Physician experts were consulted to estimate the resources and costs of converting patients to oral supplements. The Ministry of Health and Long-Term Care perspective was taken, and all costs are expressed in 2013 Canadian dollars. RESULTS: The budget impact analysis demonstrated costs of $2.8 million to the Ministry of Health and Long-Term Care in the first year of conversion; however, in subsequent years there are savings of $4.2 million per year. The cumulative 5-year budget impact demonstrates savings of $14.2 million to the health care system. LIMITATIONS: This analysis represents the cost of conversion for those currently receiving intramuscular injections. There are no conversion costs for those who are prescribed oral supplements as an initial therapy, and so the savings could be even greater than reported. As well, an underlying assumption of this analysis is that patients will comply with oral supplementation. CONCLUSIONS: Over 5 years, there are savings of $14.2 million to the health care system from switching to vitamin B12 oral supplements. PLAIN LANGUAGE SUMMARY: Vitamin B12 deficiency has long been thought to be associated with dementia and other neurocognitive disorders. In a separate report, Health Quality Ontario (HQO) reviewed the published research on this issue and found only weak evidence that vitamin B12 deficiency is associated with the onset of dementia. That review also found moderate evidence that treatment with vitamin B12 does not improve dementia and that oral supplements are as effective as injections of vitamin B12. In 2010, more than 2.9 million serum vitamin B12 tests were performed in Ontario at a cost of $40 million. Each year, approximately 110,000 residents receive vitamin B12 injections to boost their levels of vitamin B12. HQO commissioned an economic analysis to estimate the cost savings of switching from vitamin B12 injections to high-dose oral supplements for patients aged 18 years and older with confirmed B12 deficiency. This study concluded that the Ontario health care system could save $14.5 million in 5 years by switching to oral supplements, assuming that patients took the oral supplements as required.

[Peri-pregnancy folic acid supplementation must be improved]. / Foliumzuursuppletiebeleid bij zwangerschap werkt, maar moet beter.

The correct usage of folic acid (FA) supplements to prevent neural tube defects (NTDs) increased from 28% in 1996 to 50% in 2005 and remained stable until 2009. Recent data from national birth defect registries show a decrease of NTD prevalence from 13.2 (per 10,000) in 1997 to 8.3 in 2005 and stabilization up to 2009. It is estimated that between 2005 and 2009 FA supplementation prevented 583 NTD cases. The medical costs thus averted are € 75 M. If the correct usage of FA were to be increased to 70%, another 34 cases per year could be prevented. Part of the gain from continued prevention and other averted costs should be invested beforehand in the promotion of FA supplement usage.

The effect of 90 day administration of a high dose vitamin B-complex on work stress.

OBJECTIVE: Occupational stress is increasing in Western societies and the impact is significant at a personal, organisational and community level. The present study examined for the first time the efficacy of 3 months administration of two forms of high dose vitamin B complex on mood and psychological strain associated with chronic work stress. METHOD: Sixty participants completed the 3-month, double-blind, randomised, placebo-controlled trial in which personality, work demands, mood, anxiety and strain were assessed. RESULTS: After individual differences in personality and work demands were statistically controlled, the vitamin B complex treatment groups reported significantly lower personal strain and a reduction in confusion and depressed/dejected mood after 12 weeks. There were no treatment-related changes in other measures of mood and anxiety. DISCUSSION: The results of the study are consistent with two previous studies examining multivitamin supplementation and personal (non-work) feelings of strain and suggestive of significant decreases in the experience of workplace stress after 90 day supplementation of a B multivitamin. CONCLUSION: Given the direct and indirect costs of workplace stress, these findings point to the utility of a cost-effective treatment for the mood and psychological strain effects of occupational stress. These findings may have important personal health, organisational and societal outcomes given the rising cost and incidence of workplace stress.

Economic burden of neural tube defects and impact of prevention with folic acid: a literature review.

Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most countries. To understand the economic burden of NTDs and the economic impact of preventing NTDs with folic acid, a systematic review was performed on relevant studies. A total of 14 cost of illness studies and 10 economic evaluations on prevention of NTDs with folic acid were identified. Consistent findings were reported across all of the cost of illness studies. The lifetime direct medical cost for patients with NTDs is significant, with the majority of cost being for inpatient care, for treatment at initial diagnosis in childhood, and for comorbidities in adult life. The lifetime indirect cost for patients with spina bifida is even greater due to increased morbidity and premature mortality. Caregiver time costs are also significant. The results from the economic evaluations demonstrate that folic acid fortification in food and preconception folic acid consumption are cost-effective ways to reduce the incidence and prevalence of NTDs. This review highlights the significant cost burden that NTDs pose to healthcare systems, various healthcare payers, and society and concludes that the benefits of prevention of NTDs with folic acid far outweigh the cost. Further intervention with folic acid is justified in countries where the full potential of folic acid to reduce the risk of NTDs has not been realized.

Cost-effectiveness of mandatory folate fortification v. other options for the prevention of neural tube defects: results from Australia and New Zealand.

OBJECTIVE: To provide input to Australian and New Zealand government decision making regarding an optimal strategy to reduce the rate of neural tube defects (NTD). DESIGN: Standard comparative health economic evaluation techniques were employed for a set of intervention options for promoting folate/folic acid consumption in women capable of or planning a pregnancy. Evidence of effectiveness was informed by the international literature and costs were derived for Australia and New Zealand. RESULTS: Population-wide campaigns to promote supplement use and mandatory fortification were the most effective at reducing NTD, at an estimated 36 and 31 fewer cases per annum respectively for Australia and New Zealand, representing an 8 % reduction in the current annual NTD rate. Population-wide and targeted approaches to increase supplement use were cost-effective, at less than $AU 12,500 per disability-adjusted life year (DALY) averted ($US 9893, pound 5074), as was extending voluntary fortification. Mandatory fortification was not cost-effective for New Zealand at $AU 138,500 per DALY ($US 109 609, pound 56,216), with results uncertain for Australia, given widely varying cost estimates. Promoting a folate-rich diet was least cost-effective, with benefits restricted to impact on NTD. CONCLUSIONS: Several options for reducing NTD appear to fall well within accepted societal cost-effectiveness norms. All estimates are subject to considerable uncertainty, exacerbated by possible interactions between interventions, including impacts on currently effective strategies. The Australian and New Zealand governments have decided to proceed with mandatory fortification; it is hoped they will support a rigorous evaluation which will contribute to the evidence base.

Oral or intramuscular vitamin B12?

Vitamin B(12) deficiency is common, becoming more so with age, and estimates of its population prevalence have ranged from 1.5% to 15%. If untreated, it can lead to megaloblastic anaemia and irreversible neurological complications. In the UK, the usual treatment is regular intramuscular injections of hydroxocobalamin. High-dose oral vitamin B(12) replacement is standard practice in some other countries and less costly. Here we review issues around adopting an oral vitamin B(12) replacement regimen more widely in the UK.

Economic evaluation of a neural tube defect recurrence-prevention program.

BACKGROUND: Women with a pregnancy affected by a neural tube defect (NTD) are encouraged to take folic acid prior to a subsequent pregnancy, but it is unknown whether organized attempts to identify and counsel such women to prevent recurrent NTDs are cost effective. METHODS: Data from the South Carolina recurrence-prevention program for October 2001-September 2002 were analyzed between October 2002 and December 2003 to calculate costs. Cost-effectiveness modeling of the program during 1992-2006 was conducted during 2007. Results were calculated for three scenarios based on recurrence risk, supplement use, and the effectiveness of folic acid in preventing recurrences. For each scenario, quality-adjusted life years (QALYs) were calculated separately using prevented NTD-affected live births; prevented NTD-affected births (including fetal deaths); and all prevented NTD-affected pregnancies. RESULTS: The prevention program cost approximately $155,000 per year in 2003 dollars to protect 35 pregnancies and prevent approximately one NTD. The direct costs associated with an NTD depend on type and outcome, but are approximately $560,000 in 2003 dollars for a live birth with spina bifida. The base-case cost-effectiveness ratio was $39,600 per QALY gained from avoided NTD-affected live births and stillbirths, and $14,700 per QALY gained from the avoidance of all NTD-affected pregnancies. The baseline NTD recurrence risk and the use of folic acid supplements by women who are at high risk for an NTD-affected pregnancy were influential parameters. CONCLUSIONS: The South Carolina NTD recurrence-prevention program appears comparable in cost effectiveness to other preventive services. Other states might consider including NTD recurrence prevention in birth defect-prevention programs.

Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis.

This paper addresses the potential economic benefits of chromium picolinate plus biotin (Diachrome) use in people with Type 2 diabetes (T2DM). The economic model was developed to estimate the impact on health care systems' costs by improved HbA1C levels with chromium picolinate plus biotin (Diachrome). Lifetimes cost savings were estimated by adjusting a benchmark from the literature, using a price index to adjust for inflation. The cost of diabetes is highly dependent on the HbA1C level with higher initial levels and higher annual increments increasing the cost. Improvement in glycemic control has proven to be cost-effective in delaying the onset and progression of T2DM, reducing the risk for diabetes-associated complications and lowering utilization and cost of care. Chromium picolinate plus biotin (Diachrome) showed greater improvement of glycemic control in poorly controlled T2DM patients (HbA(1C) > or = 10%) compared to their better controlled counterparts (HbA(1C) < 10%). This improvement was additive to that achieved by oral hypoglycemic medications and correlates to calculated levels of cost savings. Average 3-year cost savings for chromium picolinate plus biotin (Diachrome) use could range from 1,636 dollars for a poorly controlled patient with diabetes without heart diseases or hypertension, to 5,435 dollars for a poorly controlled patient with diabetes, heart disease, and hypertension. Average 3-year cost savings was estimated to be between 3.9 billion dollars and 52.9 billion dollars for the 16.3 million existing patients with diabetes. Chromium picolinate plus biotin (Diachrome) use among the 1.17 million newly diagnosed patients with T2DM each year could deliver lifetime cost savings of 42 billion dollars, or 36,000 dollars per T2DM patient. Affordable, safe, and convenient, chromium picolinate plus biotin (Diachrome) could prove to be a cost-effective complement to existing pharmacological therapies for controlling T2DM.