Day: July 7, 2022

Categories : PaediatricsTags :

ADHD Overdiagnosis Common and Racially Skewed, US Study Finds

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Children in classroom
Photo by CDC

A study in the Journal of Learning Disabilities examining overdiagnosis of attention-deficit/hyperactivity disorder (ADHD) found that diagnoses are common in children who are functioning well, and that there is a racial bias.

ADHD overdiagnosis and subsequent overtreatment poses needless potential harm to children. It also contributes to scepticism toward those who do have moderate or severe symptoms and significant impairments, resulting in less supportive care.

Yet which sociodemographic groups of children are overdiagnosed and overtreated for ADHD is poorly understood. As a proxy for overdiagnosis, researchers selected elementary schoolchildren who had displayed above-average levels of independently assessed behavioural, academic, or executive functioning the year prior to their initial ADHD diagnoses and who did not have prior diagnostic histories. This suggested they were unlikely to have ADHD.

The researchers conducted descriptive and logistic regression analyses of a population-based subsample of 1070 elementary schoolchildren.

Among these children, (a) 27% of White children versus 19% of non-White children were later diagnosed with ADHD and (b) 20% of White children versus 14% of non-White children were later using medication. In adjusted analyses, White children are more likely to later be diagnosed (odds ratio [OR] range = 1.70–2.62) and using medication (OR range = 1.70–2.37) among those whose prior behavioural, academic, and executive functioning suggested that they were unlikely to have ADHD.

The findings also skewed toward older children, and differences in diagnoses according to race was not linked to socioeconomic status. The authors acknowledge limitations such as a small sample size as well as not being able to account for English-speaking versus non-English speaking families, but note that their results are significant for 9 out of the 10 tests used.

The researchers suggest that greater overdiagnosis in White children may be in part explained by greater access to better-resourced schools more likely to pick up (or attempt to pick up) ADHD in children. Non-White children may also need to display behaviours more consistent with ADHD to be referred for evaluation and treatment.

Cultural misconceptions about ADHD are less likely to be prevalent in non-White families, and there is evidence to suggest that ADHD overdiagnosis is being used to gain academic achievement.

They concluded: “Preventing or reducing ADHD overdiagnosis and overtreatment should contribute to more appropriate care, limit increasing ADHD prevalence, increase the academic and behavioural functioning of elementary schoolchildren being diagnosed with ADHD but who are displaying few or mild symptoms, reduce unnecessary exposure to adverse side effects of medication use, and better allocate limited mental health resources.”

Categories : Pain ManagementTags :

New Monoclonal Antibody Eptinezumab Success in Hard-to-treat Migraine

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A trial for a new monoclonal antibody, eptinezumab, in the treatment of resistant migraine has demonstrated that it significantly reduced migraine days with acceptable safety and tolerability. The findings were published in The Lancet.

Eptinezumab, which targets calcitonin gene-related peptide, has shown migraine preventive effects starting the day following infusion and acceptable safety and tolerability in phase 3 trials, but benefits in the subpopulations of patients with previous preventive treatment failures were not examined.

In the 24-week double-blind placebo-controlled DELIVER phase 3b trial, the researchers recruited adults with episodic or chronic migraine with at least four monthly migraine days and two-to-four previous preventive treatment failures within the past 10 years. Patients were randomised to either eptinezumab 100mg, eptinezumab 300mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (captured using a daily electronic diary) in weeks 1–12, assessed in the full analysis set. All participants and study personnel were masked to study drug assignments. A 48-week dose-blinded extension period is ongoing.

In all, 865 patients completed the placebo-controlled period. Compared to baseline, weeks 1–12 saw reductions of 4.8 mean monthly migraine days with eptinezumab 100mg and 5.3 days at 300mg, which was a significantly less than the reduction of 2.1 days with placebo.

Adverse events were reported in 42% of patients in the eptinezumab 100mg group, 41% in the 300mg group, and in 40% in the placebo group. COVID was the most common treatment-emergent adverse event. Serious adverse events were uncommon (five [2%] of 299 in the 100mg group, seven [2%] of 294 in the 300mg group, four [1%] of 298 in the placebo group) and included anaphylactic reaction (eptinezumab 300 mg n=2) and COVID-19 (eptinezumab 100 mg n=1 and eptinezumab 300 mg n=1).

In adults with migraine and two-to-four previous preventive treatment failures, eptinezumab provided significant migraine preventive effects compared with placebo, with acceptable safety and tolerability, indicating that eptinezumab might be an effective treatment option for this patient population. The trial has a dose-blinded extension period which will provide additional long-term safety data in patients with migraine and previous preventive treatment failures.

Categories : Mental HealthTags :

Forced Retirement a Major Factor in Physician Suicides

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Phot by Mulyadi on Unsplash

Forced retirement is a major factor when it comes to physician suicides, according to a study by Dr Kristin Kim and colleagues. Physicians also neglect to discuss physical health concerns as work stressors, the authors noted, but these are still detrimental to wellbeing – especially when it renders physicians unable to work.

The study was published in the journal Suicide and Life-Threatening Behavior.

“Medicine must dispel the myth of never-ill physicians who place the needs of their patients before their own to the detriment of their own health.”

Kim et al., 2022

While physicians are known to be more likely than non-physicians to experience work-related stressors prior to suicide, the specific nature of these stressors was not known. The present study therefore aimed to better characterise job-related problems prior to physician suicide.

Using a mixed methods approach, researchers combined thematic analysis and natural language processing to develop themes representing death investigation narratives of 200 physician suicides with implicated job problems in the National Violent Death Reporting System database between 2003 and 2018.

The thematic analysis identified six overarching themes: incapacity to work due to deterioration of physical health, substance use jeopardising employment, interaction between mental health and work-related issues, relationship conflict affecting work, legal problems leading to work-related stress, and increased financial stress. Natural language processing analysis confirmed five of these themes and elucidated important subthemes.

Clinicians often neglect physical health when identifying work stressors, but poor physical health affects work performance and increases work stress, the authors said, noting that legal and psychological supports, particularly during malpractice investigations and “fit for duty” evaluations, are sorely needed.

“Medicine must dispel the myth of never-ill physicians who place the needs of their patients before their own to the detriment of their own health,” the researchers wrote.

First author Kristen Kim, MD, told Medpage Today that she hopes that this research will help physicians “give ourselves permission to attend to those needs … to prevent the dire consequences that we may see.”

The findings highlight the importance of bolstering systemic support for physicians experiencing job problems associated with their physical and mental health, substance use, relationships, legal matters, and finances in suicide prevention efforts.

Categories : Diet and NutritionTags :

Vitamin D ‘Overdoses’ are Possible – and Dangerous

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Vitamin D pills
Photo by Michele Blackwell on Unsplash

Doctors have warned that it it is possible to ‘overdose’ on Vitamin D, with harmful effects, after they treated a man hospitalised for excessive Vitamin D intake, a case which was detailed in BMJ Case Reports.

They further stress that ‘hypervitaminosis D’ is on the increase, and linked to a wide range of potentially serious health issues.

The case concerns a middle-aged man who was referred to hospital by his family GP after complaining of recurrent vomiting, nausea, abdominal pain, leg cramps, tinnitus, dry mouth, increased thirst, diarrhoea, and weight loss (12.7 kg). 

The patient had been experiencing these symptoms had for almost three months, which had started around one month after he began an intensive vitamin supplement regimen on the advice of a nutritional therapist.

The man had had a number of health issues, including tuberculosis; a left vestibular schwannoma, resulting in deafness in that ear, hydrocephalus; bacterial meningitis; and chronic sinusitis.  

He had been taking high doses of more than 20 over the counter supplements every day containing: vitamin D 50 000mg – the daily requirement is 600mg or 400IU; vitamin K2 100mg (daily requirement 100–300 μg); vitamin C, vitamin B9 (folate) 1000mg (daily requirement 400 μg); vitamin B2 (riboflavin), vitamin B6, omega-3 2000mg twice daily (daily requirement 200–500 mg), plus several other vitamin, mineral, nutrient, and probiotic supplements.

Once he developed symptoms, he stopped taking his daily supplement cocktail, but his symptoms didn’t go away.

Blood test results from his family doctor revealed that he had very high levels of calcium and slightly raised levels of magnesium. And his vitamin D level was seven times over the level required for sufficiency.

The tests also indicated acute kidney injury. The results of various x-rays and scans to check for cancer were normal. 

The man was hospitalised for 8 days, during which time he was given intravenous fluids to flush out his system and treated with bisphosphonates – ordinarily used to treat osteoporosis or hypercalcaemia.

Two months post-discharge, his calcium level had returned to normal, but his vitamin D level was still abnormally high.

“Globally, there is a growing trend of hypervitaminosis D, a clinical condition characterised by elevated serum vitamin D3 levels,” with women, children and surgical patients most likely to be affected, the authors noted. 

Recommended vitamin D levels can be obtained through diet, sunlight exposure to sunlight, and supplements.

“Given its slow turnover (half-life of approximately two months), during which vitamin D toxicity develops, symptoms can last for several weeks,” the authors warned.

Hypervitaminosis D has many and varied symptoms, they point out, and are mostly caused by hypercalcaemia. They include drowsiness, confusion, apathy, psychosis, depression, stupor, coma, anorexia, abdominal pain, vomiting, constipation, peptic ulcers, pancreatitis, hypertension, abnormal heart rhythm, and kidney abnormalities, including renal failure. 

Other associated features, such as keratopathy (inflammatory eye disease), joint stiffness (arthralgia), and hearing loss or deafness, have also been reported, they add.

This is just one case, and while hypervitaminosis D is on the rise, it is still relatively uncommon, the authors cautioned.

Nevertheless, complementary therapy, including the use of dietary supplements, is popular, and people may not realise that it’s possible to overdose on vitamin D, or the potential consequences of doing so, they say.

“This case report further highlights the potential toxicity of supplements that are largely considered safe until taken in unsafe amounts or in unsafe combinations,” they concluded.

Source: The BMJ

Categories : CancerTags :

Topping up Mitochondrial Content to Fight Kidney Cancer

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Researchers at Karolinska Institutet in Sweden have linked resistance to treatment for VHL syndrome-induced kidney cancer to low mitochondrial content in the cell. When the researchers increased the mitochondrial content with an inhibitor, the cancer cells responded to the treatment. Their findings, which are published in Nature Metabolism, may lead to more targeted cancer drugs.

Mitochondria are the most oxygen-demanding component of the cell, but it was not known how mitochondria adapt in a low-oxygen environment and how they are linked to cancer therapy resistance.

“We’ve shown for the first time how the formation of new mitochondria is regulated in cells that lack oxygen and how this process is altered in cancer cells with VHL mutations,” explained Associate Professor Susanne Schlisio, group leader at the Karolinska Institutet.

A gene called von Hippel-Lindau (VHL) prevents healthy cells from turning cancerous. The 2019 Nobel Prize in Physiology or Medicine was awarded to the discovery that VHL was part of the cell’s oxygen detection system. Normally, VHL breaks down another protein called HIF – but when VHL is mutated, HIF accumulates and causes a disease called VHL syndrome in which the cells react as if they were lacking oxygen. This syndrome greatly increases the risk of tumours, both benign and malignant. VHL syndrome-induced kidney cancer has a poor prognosis, with a five-year survival rate of just 12%.

Researchers analysed the protein content of cancer cells from patients with different variants of VHL syndrome, to see how they differed from another group of individuals with a special VHL mutation called Chuvash, a mutation involved in hypoxia-sensing disorders without any tumour development. Those with the Chuvash VHL-mutation had normal mitochondria in their cells, while those with VHL syndrome mutation had few.

To increase the amount of mitochondrial content in VHL related kidney cancer cells, the researchers treated these tumours with an inhibitor of a mitochondrial protease called “LONP1.” This resulted in the cells becoming susceptible to the cancer drug sorafenib, which they had previously resisted. In mouse studies, this combination treatment led to reduced tumour growth.

The study’s first author Shuijie Li, postdoctoral researcher in the Schlisio’s group, suggested that the findings could be applied to more than just VHF syndromic kidney cancers.

“We hope that this new knowledge will pave the way for more specific LONP1 protease inhibitors to treat VHL-related clear cell kidney cancer,” Dr Li said. “Our finding can be linked to all VHL syndromic cancers, such as the neuroendocrine tumours pheochromocytoma and paraganglioma, and not just kidney cancer.”

Source: Karolinska Institutet