https://www.physics-astronomy.com/2022/03/zeno-effect-verified-atoms-wont-move.html?m=1
Day: 03/01/2022
Ultrasound Scan Can Diagnose Prostate Cancer
Could diet help protect against severe COVID-19?
Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction: a systematic review and economic evaluation.
Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins.
OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction.
METHODS: A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate.
RESULTS: A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectiveness analysis produced incremental costs of £4878, incremental quality-adjusted life-years of 1.34 and an incremental cost-effectiveness ratio of £3650. Probabilistic sensitivity analyses showed that at thresholds of £20,000 and £30,000 per quality-adjusted life-year coenzyme Q10 had a high probability (95.2% and 95.8%, respectively) of being more cost-effective than standard care alone. Scenario analyses in which the population and other model assumptions were varied all found coenzyme Q10 to be cost-effective. The expected value of perfect information suggested that a new trial could be valuable.
LIMITATIONS: For most outcomes, data were available from few trials and different trials contributed to different outcomes. There were concerns about risk of bias and whether or not the results from included trials were applicable to a typical UK population. A lack of individual participant data meant that planned detailed analyses of effect modifiers were not possible.
CONCLUSIONS: Available evidence suggested that, if prescribed, coenzyme Q10 has the potential to be clinically effective and cost-effective for heart failure with a reduced ejection fraction. However, given important concerns about risk of bias, plausibility of effect sizes and applicability of the evidence base, establishing whether or not coenzyme Q10 is genuinely effective in a typical UK population is important, particularly as coenzyme Q10 has not been subject to the scrutiny of drug-licensing processes. Stronger evidence is needed before considering its prescription in the NHS.
Switching generic levothyroxine preparations does not affect thyroid hormone levels
Adults who switch generic levothyroxine preparations from one manufacturer to another do not have a difference in mean thyroid-stimulating hormone levels compared with those who do not switch, according to study data.
According to guidelines published by the American Thyroid Association in 2014, providers are advised to avoid switching among generic levothyroxine products from different manufacturers. Juan P. Brito, MD, MSc, associate professor of medicine and consultant in the division of endocrinology at the Mayo Clinic in Rochester, Minnesota, said the guidelines have led providers to prescribe brand-name levothyroxine for most adults with hypothyroidism because physicians are unable to keep track of when pharmacies switch generic products.
“We decided to do this study to test whether switching among generic levothyroxine products have any effect on thyroid hormone values,” Brito told Healio. “In those who switch, we don’t see an impact on thyroid hormone levels compared with people who did not switch. This sends a signal that switching is safe and keeping patients on generic levothyroxine doesn’t have a significant impact on thyroid hormone values.”
Brito and colleagues conducted a retrospective study of deidentified administrative claims data from 2008 to June 2019 in the OptumLabs Data Warehouse, a database that includes people enrolled in commercial insurance and Medicare Advantage programs across the U.S. Researchers included 15,829 adults who filled a generic levothyroxine prescription from Mylan, Sandoz or Lannett (mean age, 58.9 years; 73.4% women, 71.4% white). Adults with a stable prescription dose from the same manufacturer and a normal TSH level between 0.3 mIU/L and 4.4 mIU/L for at least 3 months were included in the analysis. TSH levels were collected from those who used the same generic prescription from a random fill date within a year of their first fill data, and from the date of switching for adults who changed preparations.
The findings were published in JAMA Internal Medicine.
Of the study cohort, 82.4% continued taking the same generic preparation during the study period, and 17.6% switched at least once. The 2,780 adults who switched were paired with an adult in the nonswitching group using propensity score-matching. Among the matched pairs, the percentage of adults with a normal TSH between 0.3 mIU/L and 4.4 mIU/L was similar between switchers (84.5%) and nonswitchers (82.7%). Similarly, the proportion of adults with markedly abnormal TSH levels of less than 0.1 mIU/L or greater than 10 mIU/L was similar for switchers (2.5%) and nonswitchers (3.1%). Mean TSH levels were 2.7 mIU/L in both groups.
In a subgroup of 364 adults receiving more than 100 g of levothyroxine daily, there was no significant difference between switchers and nonswitchers in the percentage of those with normal TSH levels. There were also no associations observed in sensitivity analysis.
Brito said the findings provide evidence for the ATA to update its recommendations to allow generic levothyroxine switching, noting the change can have a significant cost savings for patients currently taking brand-name preparations.
“Levothyroxine is one of the most prescribed medications in the U.S.,” Brito said. “It’s a huge market, and prescribing only brands is a significant expense to the health care system and the patients as well.
“Clinicians should not give patients a brand name just because they have concerns about switching,” Brito added. “They should revise the recommendation that we keep the patients on the same product.”
COVID‐19 mRNA vaccine (Comirnaty)‐induced myocarditis
Clinical record
A 20‐year‐old man presented to hospital with 3 days of pleuritic chest pain, fevers and diaphoresis. Past medical history was significant for asthma and depression. Medications included fluticasone–salmeterol and mirtazapine. He had no personal or family history of myocarditis or inflammatory disorders. He was a non‐smoker with social alcohol intake, and did not report having used illicit drugs.
Symptom onset occurred 12 hours after administration of his second dose of the Pfizer (Comirnaty) coronavirus disease 2019 (COVID‐19) vaccine, with headaches, night sweats and chills. He developed chest pain at 48 hours. The first dose of the vaccine was administered 23 days before the second dose and was uncomplicated.
On presentation, he was febrile (38.1°C) and had tachycardia (130 beats/min). An electrocardiogram (ECG) revealed sinus tachycardia with global ST elevation (Box 1). His initial troponin level was 3557 ng/L (reference interval [RI], < 26 ng/L), peaking at 9853 ng/L 3 hours later. His C‐reactive protein concentration was elevated at 50.9 mg/L (RI, < 5.0 mg/L) and erythrocyte sedimentation rate was 45 mm/h (RI, 1–19 mm/h). Full blood examination, biochemistry and liver function results were all normal. Septic screening (chest x‐ray and urine and blood cultures) was negative. A SARS‐CoV‐2 nucleic acid test result was also negative, and a limited vasculitic screen was unremarkable.
Box 1
Electrocardiogram showing sinus tachycardia with widespread ST elevation
Transthoracic echocardiography showed normal biventricular function with no pericardial effusion. Cardiac magnetic resonance imaging showed normal left ventricular size and mildly impaired systolic function with hypokinesis of the mid and apical lateral segments associated with epicardial late gadolinium enhancement (Box 2), consistent with myocarditis.
Box 2
Cardiac magnetic resonance image showing epicardial late gadolinium enhancement over the mid and apical lateral segments (arrow)
He was commenced on ibuprofen 400 mg three times a day, pantoprazole 40 mg daily (to reduce risk of gastritis), and bisoprolol 2.5 mg daily, with complete resolution of symptoms within 24 hours. No rhythm disturbances were detected on telemetry and he was discharged after 48 hours. He was advised to avoid strenuous activity and scheduled for repeat transthoracic echocardiography in 3 months.
Discussion
Myocarditis is a known complication of SARS‐CoV‐2 infection occurring in 0.3–2.3% of patients.1 However, there has been emerging evidence of myocarditis following COVID‐19 messenger RNA (mRNA)‐based vaccinations (Pfizer [Comirnaty] and Moderna [Spikevax] vaccines). By 2 January 2022, 415 cases of myocarditis temporally related to Pfizer (Cominarty) COVID‐19 mRNA vaccination had been reported to the Therapeutic Goods Administration,2 although not all may be attributable to the vaccine.
COVID‐19 mRNA vaccine‐related myocarditis is more common in males, younger patients and following the second or subsequent dose. A US Centers for Disease Control and Prevention summary described the highest incidence of myocarditis in males aged 12–29 years, with 40.6 per million males affected following the second dose, compared with only 4.2 per million females aged 12–29 years. Rates decreased to 2.4 and 1.0 per million in males and females aged over 30 years, respectively.3 Notably, the background incidence of myocarditis in the general population aged 18–34 years is estimated at 37 per 100 000 patient years in males and 16 per 100 000 patient years in females.2 Among 1226 cases of mRNA vaccination‐related myocarditis, no deaths were reported.3
In a recent case series, all 61 patients diagnosed with COVID‐19 vaccination‐related myocarditis had mild presentations with chest pain and troponinaemia mostly within 3 days of vaccination.4 The vast majority (87%) had ECG abnormalities, most commonly ST‐segment elevation, and all had cardiac magnetic resonance imaging findings, most commonly late gadolinium enhancement. Left ventricular dysfunction occurred in around one‐third of patients. Treatments included non‐steroidal anti‐inflammatories, colchicine and, less commonly, steroids or intravenous immunoglobulin. Long term outcomes of COVID‐19 vaccine‐related myocarditis have not yet been described, but in this series nearly 90% of patients had symptom resolution within a median hospitalisation duration of 4.6 days.4 A case series reporting incomplete symptom resolution found seven of 23 otherwise healthy military members with vaccine‐related myocarditis had ongoing chest discomfort but were otherwise well enough for discharge.5
COVID‐19 mRNA vaccine‐related myocarditis is an extremely rare and mild complication, and is much less frequent than myocarditis secondary to SARS‐CoV‐2 infection. In the setting of potential myocarditis or pericarditis, current Australian guidelines suggest management in the primary care or outpatient setting is appropriate if presentation is mild and if ECG, troponin and inflammatory markers can be reviewed within 12 hours. If the patient is unwell, has chest pain and is aged over 30, or if ECG findings are abnormal, emergency department referral is recommended. Confirmed myocarditis or pericarditis may require brief hospitalisation for cardiac monitoring, or cardiology referral for additional investigations.2
Given the scarcity, mild presentation and clinical course of mRNA vaccine‐related myocarditis, and the efficacy of vaccines in reducing SARS‐CoV‐2 infection, the benefit–risk assessment for COVID‐19 mRNA vaccination is still overwhelmingly favourable for all age and sex groups, including young people.4
Lessons from practice
- • COVID‐19 mRNA vaccine‐related myocarditis is an extremely rare side effect that is most common in males aged 12–29 years, after the second vaccine dose.
- • Symptoms are usually mild, requiring only brief hospitalisation, and treatments are readily available.
- • Initial review and work‐up may occur in the outpatient setting if patients are young (< 30 years), clinically stable and investigation results can be obtained in a timely manner. Confirmed myocarditis or pericarditis may involve emergency department review, hospitalisation and/or cardiology referral.
- • COVID‐19 vaccinations (including boosters) are crucial in reducing the spread and severity of infection. The incidence and severity of COVID‐19‐related myocarditis is higher than vaccine‐related myocarditis. Thus, vaccine‐related myocarditis should not impede vaccination efforts.
Mitochondrial donation: is Australia ready?
Legalising mitochondrial donation will present a promising path forward to reduce mitochondrial disease transmission in affected families
Australia is poised to make historic legislative changes that, for the first time, would enable couples affected by maternally inherited mitochondrial disease the opportunity of having unaffected genetically related children.
Mitochondrial diseases encompass a broad range of multi‐organ disorders, ranging from mild to life‐threatening conditions that manifest across all age groups. No cures are available, only symptomatic treatments.1 These heritable diseases are caused by the dysfunction of mitochondria — organelles that produce essential energy (adenosine triphosphate [ATP]) to power all crucial cellular functions. Energy‐demanding tissues, such as brain and muscle, are most commonly, but not exclusively, affected. Mitochondrial disorders are caused by mutations in either the mitochondria’s own DNA (mtDNA; many copies of a 16 569 base pair circular genome) or in the 3.2 billion base pair nuclear DNA (nDNA; in 46 chromosomes) present in each cell.2 Unlike nDNA, which is inherited from both parents, mtDNA is maternally inherited, and mtDNA variants cause maternally inherited mitochondrial disease (Box 1). The transmission of mutant mtDNA into individual oocytes, and subsequent distribution to different embryonic cells after fertilisation, is a complex and largely unpredictable process that continues throughout life. Most affected individuals have both normal and mutant mtDNA in each cell (known as heteroplasmy). Variable mutational loads in different individuals and different cell types result from unequal segregation of normal and mutant mtDNA as cells divide.2 Programmed reduction in mitochondrial copy number in primordial germ cells can select against particular mtDNA variants, causing a shift in heteroplasmy from one generation to the next.3,4 The cellular dysfunction caused by mtDNA mutations depends on the cell’s specific energy requirements as well as the total amount and ratio of normal to mutant mtDNA. Substantial evidence suggests that the higher the mutant mtDNA load, the higher the risk of severe disease, although there are many discrepancies.5 Over 250 pathological mtDNA mutations have been identified,1 with each likely to have their own threshold load for causing mitochondrial dysfunction.6,7 This complex and nuanced genetic transmission puts mtDNA‐mediated mitochondrial disease in a separate category of inherited genetic diseases to nDNA mutations, which are transmitted by largely predictable Mendelian genetics. Patients with mitochondrial disease require diagnosis and familial risk evaluation by highly skilled clinicians who understand this complexity.
Box 1
Common clinical syndromes caused by maternally inherited mutations in mitochondrial DNA (mtDNA)*
In Australia, the incidence of mtDNA mutations is predicted to be at least 1:250, with several hundred families already diagnosed, although many carriers remain unidentified.4,8 Some families have multiple generations of affected individuals, often with devastating consequences. Their health care needs present enormous emotional, physical, social and financial burdens on families, leading many couples to seek options to prevent disease transmission to their offspring. Their current choices include voluntary childlessness, adoption, using eggs donated by unaffected women, or prenatal and pre‐implantation genetic diagnosis. For couples wanting to have genetically related children, prenatal and pre‐implantation genetic diagnosis are not reassuring options because all of the woman’s oocytes may produce embryos with high levels of mutant mtDNA in some cells.9 Recent developments in mitochondrial donation now present a promising path forward to reduce disease transmission in these families by replacing faulty mitochondria containing mutant mtDNA with healthy mitochondria containing normal mtDNA.10 To ensure all cells of the offspring contain healthy mitochondria, this replacement must be done at the one‐cell stage of conception, using procedures to manipulate mature or newly fertilised oocytes that are currently prohibited under Australian legislation. After lengthy and extensive scientific review and public consultation, the United Kingdom changed its legislation in 2015 to allow mitochondrial donation under specified regulation.11 Following this lead, the Australian Senate initiated an inquiry in 2018 to consider the appropriateness of the technology in the Australian context. A Citizens’ Jury and a National Health and Medical Research Council (NHMRC) Mitochondrial Expert Working Committee and Citizens’ Panel facilitated wide‐ranging community consultation12,13 over 3 years that preceded drafting of the Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021, currently under Parliamentary review. In this article, we outline the scientific and ethical issues raised by mitochondrial donation and the changes to legislation needed before its implementation in Australia.
The technology and the law
Mitochondrial donation refers to assisted reproductive technologies used to uncouple the inheritance of an affected woman’s nDNA (normal) from her mtDNA (mutant). Two techniques approved for clinical use in the UK are maternal spindle transfer (MST) and pronuclear transfer (PNT) (Box 2). Preclinical studies indicate that in both methods there may be some carry‐over of mutant mtDNA during the transfer of nDNA, but at a level unlikely to cause severe disease in the offspring.14 In the single live birth so far reported, using MST, the low levels of mtDNA found in newborn tissues were well below the threshold for risk of the particular mitochondrial disease.15
Box 2
Schematic drawing showing techniques of maternal spindle transfer (MST) and pronuclear transfer (PNT) to generate embryos unaffected by maternally inherited mitochondrial disease*
In Australia, the Prohibition of Human Cloning for Reproduction Act 2002 (the Act) prohibits the creation of a human embryo containing genetic material from more than two persons and bans the alteration of a genome of a human cell where that alteration is heritable through the germline. Since mtDNA is heritable through female gametes, the utilisation of a donor oocyte in mitochondrial donation means that genetic material from three persons is used to create the embryo (Box 2). However, mtDNA makes no contribution to the characteristics of an individual other than cellular bioenergetics. Moreover, unlike nDNA, mtDNA sequences are not unique to an individual but are shared by mothers and all their offspring, making mtDNA an identifier of families (through the maternal line) rather than individuals. There is a scientific view that a woman donating oocytes for mitochondrial donation does not contribute genetic material to the child’s unique genomic identity. Moreover, scientists consider that transfer of nDNA between oocytes does not constitute alteration of the genome, even though this replacement is heritable, since neither nDNA nor mtDNA are modified in any way. UK legislation refers specifically to nuclear DNA from the contributing eggs in the processes that are permitted under the regulation.10 The extensive consultation undertaken in Australia indicates mixed views on these matters. Maeve’s Law has been drafted to permit mitochondrial donation by exemption to the provisions of the Act, with strict regulation under a licensing framework to be administered by the NHMRC Embryo Research Licensing Committee.
The ethical and regulatory framework
While the potential benefits of mitochondrial donation for many families are well recognised, concerns remain about ethical risks. Apart from religious and moral views regarding interventions using assisted reproductive technologies in the formation of human life, the primary ethical concerns are about the rights of the children and oocyte donors and long term safety of the procedure for offspring born.13 Australia recognises the rights of children born from assisted reproductive technologies to know their genetic origins, and this right would extend to information about individuals donating oocytes for mitochondrial donation. Such access would need to be strictly controlled to protect the privacy of donors. While substantial pre‐clinical studies indicate the procedures are feasible and safe enough for clinical implementation, evidence of true efficacy is limited since only one live birth has so far been reported in the public domain. It is, however, recognised by scientists and clinicians that further technical refinements are needed to minimise the carry‐over of mutant mtDNA, as even very low levels of certain mtDNA mutations carry risks of severe or late onset disease in the individual or selective transmission to their offspring.4 As with any new medical technology, further testing and refinement can be achieved most effectively in a clinical setting. The UK Parliament took a cautionary approach in allowing the procedure in licensed centres for stringently selected high risk cases with a requirement for follow‐up and reporting of outcomes.11 A similar but even more cautious approach is being proposed for Australia. If passed by Parliament, Maeve’s Law will enable a staged implementation of mitochondrial donation, with licensing for research and training and a clinical trial over 10 years to provide evidence of safety and efficacy before approval is given for clinical use.
Australia has a long history in, and an excellent regulatory environment for, procedures involving assisted reproductive technologies, through both federal and state legislation. Clinics require accreditation through the Reproductive Technology Accreditation Committee and must comply with the NHMRC Ethical guidelines on the use of assisted reproductive technology in clinical practice and research.16 Applications to develop new procedures need approval by the NHMRC Embryo Research Licensing Committee, which would regulate licenses for mitochondrial donation, guided by clinical experts. Australia has the clinical expertise in mitochondrial disease to evaluate and select eligible families, and provide clinical oversight of mitochondrial donation. Eligible couples and oocyte donors will require expert counselling to ensure they do not have unrealistic expectations about the outcomes, understand the rights of any offspring to know their genetic history, and can make informed decisions regarding their reproductive options.
Conclusions
Mitochondrial donation can significantly reduce the risk of maternally inherited mitochondrial disease transmission to offspring and, for some families, provides their only option to have unaffected, genetically related children. Australia has the clinical and scientific expertise to introduce mitochondrial donation in a highly regulated environment, but requires changes in legislation to adopt this innovative technology, as proposed in the Maeve’s Law currently under parliamentary review. A cautionary, staged approach is being considered for implementation in Australia. Establishment of a coordinated network of clinics forming a national service would allow equitable access to the procedure and the clinical expertise necessary to evaluate patient outcomes, provide expert follow‐up, and support research and training in this important area.
Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk
Central Illustration
Abstract
Background
Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.
Objectives
This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.
Methods
Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor–adjusted Cox regression models.
Results
Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.
Conclusions
Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.
Music therapy reduces depression, menopausal symptoms
Women who participated in music therapy had lower levels of depression and reduced menopausal symptoms compared with those who did not, according to findings in Menopause.
“Evidence suggests that the prevalence of depression increases during the menopausal transition and postmenopausal period, including middle age,” DeryaYükselKoçak, PhD, assistant professor in the department of nursing at Hitit University Faculty of Health Sciences in Çorum, Turkey, and colleagues wrote.
They noted that studies have shown music’s effect on depression and menopausal symptoms separately, though “it is noteworthy that there is no study investigating the effects of … music therapy on [both] menopausal symptoms and the risk of depression in menopausal women.”
Koçak and colleagues enrolled 48 postmenopausal women with no history of depression in a randomized controlled study from July 2019 to December 2020. At the beginning of the study, participants completed a form detailing sociodemographic information, as well as the Menopause Rating Scale (MRS) questionnaire — which assessed somatic, psychological and urogenital symptoms of menopause — and the Beck Depression Inventory (BDI). They completed the MRS and BDI again at the end of 6 weeks.
The researchers played three pieces of Turkish classical music — a genre that had “comforted and calmed” participants in a pilot study — for 21 participants (mean age, 59.1 years; mean age of menopause, 44.2 years). Participants assigned to the music therapy intervention chose their favorite song and were instructed to use headphones to listen to their chosen song for at least 15 minutes every day when they were alone in a quiet environment for 6 weeks. The 27 control participants (mean age, 56.5 years; mean age of menopause, 46.8 years) did not have any intervention.
There were no statistically significant differences in menopausal symptoms between the control and intervention groups at baseline.
MRS posttest scores of the women in the control group were higher than those in the music group, but the difference was not significant, the researchers said.
In the intervention group, MRS posttest scores overall and for three components — somatic, psychological and urogenital subscales — were 99% lower than pretest scores (P < .01), which constituted a significant decrease in menopausal symptoms. There were no significant differences between pretest and posttest median scores in the control group, however.
BDI scores showed depression was significantly decreased in the intervention group (pretest mean value, 15.38; posttest mean value, 11.81; P = .003). In the control group, there was no significant change in BDI scores.
“Although menopause is a natural process, the management of symptoms that occur during this period bears significant importance for women,” Koçak and colleagues wrote.
“The present study on music therapy and depression suggests a significant and permanent reduction in patients’ symptoms and improvement in their quality of life,” they added.
Study limitations included women’s refusal to participate, non-generalizability of findings and self-reported data.
Koçak and colleagues suggested more research on music’s effect on menopausal symptoms to validate their findings for future clinical application.
PERSPECTIVE
This study highlights the potential benefits of a simple, easy-to-implement, low-cost, low-risk intervention for common symptoms women experience during the menopause transition, including depressed mood. Although this study is small, music therapy can be added to our armamentarium of non-medication strategies for management of menopause symptoms. Additional study is needed to confirm these findings in larger and more diverse groups of women. It is also important to note that for those women who do not experience adequate relief of symptoms with this and other non-medication treatments, there are safe and effective medications for treatment of menopause symptoms, including menopausal hormone therapy.
Stephanie Faubion, MD, MBA
Director, Mayo Clinic Center for Women’s Health
Medical Director, the North American Menopause Society
Vitamin D2 supplement may slow progression of new-onset type 1 diabetes in children
A supplement of Vitamin D2 may improve insulin sensitivity and slow the increase of HbA1c for children and adolescents with new-onset type 1 diabetes, according to study findings published in the Journal of the Endocrine Society.
In findings from a randomized controlled trial, youths with type 1 diabetes randomly assigned 50,000 IU of adjunctive ergocalciferol weekly for 2 months and then biweekly for 10 months had lower serum tumor necrosis factor-alpha levels at 12 months and slower increases in both HbA1c and insulin dose-adjusted HbA1c compared with placebo.
“This 12-month randomized controlled trial found no statistically significant differences between the groups for the duration of partial clinical remission, magnitude of residual beta-cell function, insulin dose-adjusted HbA1c and glycemia,” Benjamin Udoka Nwosu, MD, professor of pediatrics at the University of Massachusetts Medical School, and colleagues wrote. “However, a statistically significantly faster rate of increase of HbA1c and insulin dose-adjusted HbA1c values in the placebo group suggested a faster rate of loss of residual beta-cell function in that group, which indicates protection of residual beta-cell function by high-dose ergocalciferol supplementation in the experimental group.”
Researchers conducted a randomized, double-blind, placebo-controlled trial comparing the effects of ergocalciferol vs. placebo in children and adolescents with new-onset type 1 diabetes. Individuals aged 10 to 21 years with type 1 diabetes duration of less than 3 months were recruited to participate. Following a run-in phase where a treat-to-target insulin regimen was implemented for 1 to 2 months, 36 participants were randomly assigned to a treatment group receiving 50,000 IU of ergocalciferol once per week for 2 months followed by every other week for 10 months, or placebo. Follow-up visits were conducted at 3, 6, 9 and 12 months. Visits took place between 8 and 10:30 a.m. following an overnight fast. Researchers collected anthropometrics, HbA1c, proinflammatory and anti-inflammatory cytokine levels, and glucose data.
The ergocalciferol group had higher concentrations of serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) compared with placebo. No differences were observed between the two groups in blood pressure, BMI z score, waist circumference, fasting C-peptide and stimulated C-peptide.
Both groups had an increase in HbA1c during the study in trend analysis. The ergocalciferol group had an increase in HbA1c of 0.14% every 3 months, lower than the placebo’s mean increase of 0.46% (P = .04). Insulin dose-adjusted HbA1c was higher in the treatment group at 3 months compared with placebo (P = .05). The ergocalciferol group had an increase in insulin dose-adjusted HbA1c of 0.3% every 3 months compared with a 0.77% increase in placebo (P = .02). At 12 months, serum tumor necrosis factor-alpha was lower in the ergocalciferol group compared with placebo (1.12 pg/mL vs. 1.32 pg/mL; P = .03).
“Adjunctive ergocalciferol supplementation statistically significantly reduced serum tumor necrosis factor-alpha concentration and significantly blunted the rates of increase both in HbA1c and insulin dose-adjusted HbA1c, suggesting a protection of residual beta-cell function and partial remission in youth with newly diagnosed type 1 diabetes,” the researchers wrote. “This suggests that ergocalciferol slowed the rise in insulin requirements by improving insulin sensitivity in youth with newly diagnosed type 1 diabetes. Larger studies are needed to quantify the effect of vitamin D on insulin sensitivity in youth with type 1 diabetes.”
ARYAN'S BLOG 