Obesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated ...with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM.
Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients.
Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.
Abstract Background Well-written and transparent case reports (1) reveal early signals of potential benefits, harms, and information on the use of resources; (2) provide information for clinical ...research and clinical practice guidelines, and (3) inform medical education. High-quality case reports are more likely when authors follow reporting guidelines. During 2011–2012, a group of clinicians, researchers, and journal editors developed recommendations for the accurate reporting of information in case reports that resulted in the CARE (CAse REport) Statement and Checklist. They were presented at the 2013 International Congress on Peer Review and Biomedical Publication, have been endorsed by multiple medical journals, and translated into nine languages. Objectives This explanation and elaboration document has the objective to increase the use and dissemination of the CARE Checklist in writing and publishing case reports. Article Design and Setting Each item from the CARE Checklist is explained and accompanied by published examples. The explanations and examples in this document are designed to support the writing of high-quality case reports by authors and their critical appraisal by editors, peer reviewers, and readers. Results and Conclusion This article and the 2013 CARE Statement and Checklist, available from the CARE website www.care-statement.org and the EQUATOR Network www.equator-network.org , are resources for improving the completeness and transparency of case reports.
IntroductionHigh prices for insulin pose a barrier to treatment for people living with diabetes, with an estimated 50% of 100 million patients needing insulin lacking reliable access. As insulin ...analogues replace regular human insulin (RHI) globally, their relative prices will become increasingly important. Three originator companies control 96% of the global insulin market, and few biosimilar insulins are available. We estimated the price reductions that could be achieved if numerous biosimilar manufacturers entered the insulin market.MethodsData on the price of active pharmaceutical ingredient (API) exported from India were retrieved from an online customs database. Manufacturers of insulins were contacted for price quotes. Where market API prices could not be identified, prices were estimated based on comparison of similarity, in terms of manufacturing process, with APIs for which prices were available. Potential biosimilar prices were estimated by adding costs of excipients, formulation, transport, development and regulatory costs, and a profit margin.ResultsThe manufacturing processes for RHI and insulin analogues are similar. API prices were US$24 750/kg for RHI, US$68 757/kg for insulin glargine and an estimated US$100 000/kg for other analogues. Estimated biosimilar prices were US$48–71 per patient per year for RHI, US$49–72 for neutral protamine Hagedorn (NPH) insulin and US$78–133 for analogues (except detemir: US$283–365).ConclusionTreatment with biosimilar RHI and insulin NPH could cost ≤US$72 per year and with insulin analogues ≤US$133 per year. Estimated biosimilar prices were markedly lower than the current prices for insulin analogues. Widespread availability at estimated prices may allow substantial savings globally.
The coronavirus disease 2019 (COVID-19) pandemic has led to significant morbidity and mortality. Although COVID-19 vaccination is available, therapeutic options are still needed. The goal of the ...present manuscript is to report on a treatment strategy used in a naturopathic medical practice for mild and moderate COVID-19.
A retrospective chart review was conducted of 30 consecutive patients diagnosed with mild and moderate COVID-19 who were provided multi-nutrient, herbal, and probiotic treatment in a rural, out-patient, naturopathic primary care setting.
The primary outcome was treatment safety; secondary outcomes included changes in symptoms, progression to severe COVID-19, incidence of long COVID, and recovery time.
No side effects or adverse events were reported from treatment and all patients experienced resolution of symptoms presumed to be associated with COVID-19 infection. One patient who had been ill for 28 days prior to presentation was hospitalized. Five patients had an illness duration of more than one month. Time to treatment was correlated with duration of illness post-treatment (r = 0.63, p < 0.001) and more symptoms at presentation was correlated with a longer duration of illness (r = 0.52, p < 0.01).
In this retrospective chart review, a multi-nutrient, herbal, and probiotic therapeutic approach for mild and moderate COVID-19 appeared to be well-tolerated. Delay in seeking treatment after symptom onset, as well as more symptoms at presentation, were correlated with a longer duration of illness. This treatment strategy may have clinical benefit, warranting prospective clinical trials with confirmed COVID-19 cases.
•Therapeutic strategies are still needed for COVID-19 infection and the potential for natural products is under-studied.•Outcomes are reported on a treatment strategy for mild and moderate COVID-19 well-tolerated in 30 patients.•Treatment included agents involved in innate and adaptive immunity and shown to be supportive in respiratory infections.•All 30 patients experienced a complete resolution of symptoms.•Time to treatment was correlated with duration of illness post-treatment, suggesting earlier intervention may be helpful.
Objective
Design and pilot test a new decision making tool for women with physical disabilities (impairment of physical function due to chronic conditions) considering pregnancy.
Data Sources and ...Study Setting
Quantitative surveys and qualitative interviews were collected from participants living in the community.
Study Design
Clinical guidelines and survey and focus group data about pregnancy informational and decisional needs guided content development. The tool was pilot tested in a 12‐week trial with participants with physical disabilities considering or actively planning a pregnancy. Feasibility outcomes were acceptability, implementation, and demand (collected at end of the trial); preliminary efficacy focused on decisional conflict and readiness (baseline, 6 weeks, and end of trial).
Data Collection
Survey data were collected using an online form. One‐on‐one interviews were conducted to learn more about experience using the tool.
Principal Findings
Thirty eight participants with mild, moderate, or severe physical disabilities participated. Feasibility outcomes indicated that the tool provided participants with information, guiding questions, and helped them to consider multiple aspects of the decision about pregnancy. Most participants responded positively to the new decision making tool, finding it easy to use and the information balanced. Feedback highlighted opportunity for improvement, such as more specific information, peer stories, and the limitations of a paper format. There was significant linear effect of time, with increased decisional certainty and readiness, values clarity, and decisional support (partial η2 90% CI = 0.310 0.08, 0.46, 0.435 0.19, 0.60, 0.134 0, 0.29, 0.178 0.01, 0.35, respectively). Decisional certainty and readiness had high observed power (96.7% and 99.3%, respectively) with lower observed power for clarity and support (60.6% and 75.1%, respectively).
Conclusions
The new tool shows promise for supporting women with physical disabilities in navigating pregnancy decision making. Future development of complementary strategies to support health care providers will help improve shared decision making and patient‐centered care.
Seven years after the introduction of direct-acting antivirals (DAAs) for the treatment of hepatitis C, high prices remain a barrier for treatment programs worldwide. This study seeks to describe ...current prices for originator DAAs in 50 countries and evaluate the relationship between prices and GDP per capita.
Data on prices of sofosbuvir, daclatasvir, sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir were collected from national databases for 50 countries. Cost-based generic prices were estimated using an established algorithm, which accounts for costs of the active pharmaceutical ingredient (API), excipients, conversion costs of API to finished pharmaceutical product, taxes assuming manufacture in India, and a 10% profit margin. Correlation between current market prices and GDP per capita was assessed by Spearman rank-order correlation.
Median originator prices per standard course were US$40,502 for sofosbuvir, US$26,928 for daclatasvir, US$46,812 for sofosbuvir/ledipasvir, US$34,381 for sofosbuvir/velpatasvir, and US$30,710 for glecaprevir/pibrentasvir (G/P). The estimated cost-based generic prices for a 12-week course were US$28 for sofosbuvir, US$31 for ledipasvir, US$58 for velpatasvir, US$4 for daclatasvir. For fixed-dose combinations, estimated cost-based prices were US$58 for sofosbuvir/ledipasvir, US$85 for sofosbuvir/velpatasvir, and US$31 for sofosbuvir/daclatasvir (API cost data were insufficient to calculate an estimate for G/P). Cumulative originator sales of WHO-recommended DAAs reached US$82 billion by the end of 2019. Across the 50 countries, there was no correlation between GDP per capita and DAA price, nor between estimated viraemic population and DAA price. Sub-analyses within World Bank income groups found a significant negative correlation between price and GDP per capita for all DAAs within the high-income countries group.
Prices of DAAs vary widely across countries. The lack of correlation between DAA price and GDP per capita and viraemic population suggests that prices for DAAs are not adjusted based on country income level or potential patient population. Among high-income countries, DAA prices fall as income levels rise, possibly due to greater negotiating power of wealthier countries. DAA prices in most countries remain many times higher than estimated cost-based generic prices.
Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically ...high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.
PDF
