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Monday, November 4, 2019

Diabetes drug relieves nicotine withdrawal

A drug commonly used to treat Type II diabetes abolishes the characteristic signs of nicotine withdrawal in rats and mice, according to new research published in JNeurosci. The finding may offer an important new strategy in the battle to quit smoking.

Smokers trying to quit face potent side effects from nicotine withdrawal, including cravings, increased appetite, restlessness, anxiety, irritability, and depression. Even though they may want to quit, many smokers continue to smoke simply because the experience is so unpleasant.

The diabetes drug, pioglitazone, targets a specific form of the peroxisome proliferator-activated receptors in the nucleus. This receptor, PPARγ, is found in areas of the brain involved in drug addiction.

Domi et al. demonstrated that direct injections of pioglitazone into the hippocampi of male mice reduced the signs of physical nicotine withdrawal, including paw tremors, chattering, and head shakes. Injecting pioglitazone into the amygdala of male mice ameliorated signs of anxiety associated with nicotine withdrawal.

Nicotine abusers face a 30% higher risk of developing Type II diabetes. The researchers suggest pioglitazone may help diabetic smokers quit by lessening the physical and emotional withdrawal symptoms while reducing insulin resistance.

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Manuscript title: Activation of PPARγ Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms Through Mechanisms Involving Amygdala and Hippocampus Neurostransmission

Please contact media@sfn.org for full-text PDF and to join SfN’s journals media list.

https://www.eurekalert.org/pub_releases/2019-11/sfn-ddr102919.php

Warren plan would cut deep into doctors’, hospitals’ pay

Democratic presidential candidate Elizabeth Warren says that to help fund her Medicare-for-all plan — which would eliminate private insurance — she would pay physicians and hospitals at roughly the current Medicare rates and aggressively negotiate discounts from pharmaceutical companies.

The Massachusetts senator claims that her plan — the details of which she released today — would cost an estimated $52 trillion over 10 years (with $20.5 trillion in new federal spending), and would also be paid for by taxing financial transactions, levying an “ultra-millionaire” tax, and reining in defense spending.

In addition, instead of paying insurance companies for workers’ healthcare — which Warren says would amount to $11 trillion over 10 years — employers would pay a $9 trillion Medicare-for-all tax.

The plan would require no new taxes on the middle class, the candidate contends.

Warren’s estimates were assembled in part by Donald Berwick, MD, president emeritus of the Institute for Healthcare Improvement and administrator of the Centers for Medicare and Medicaid Services under President Barack Obama, and Simon Johnson, Ronald A. Kurtz Professor of Entrepreneurship at the MIT Sloan School of Management.

“These experts conclude that my plan would slightly reduce the projected amount of money that the United States would otherwise spend on health care over the next 10 years, while covering everyone and giving them vastly better coverage,” Warren said.

Robert Laszewski, a long-time Washington observer with Health Policy and Strategy Associates, said, “The numbers kind of work,” but that the plan is so complex with so many moving parts that it’s politically untenable.

“I just think that there’s a zero chance that single payer is going to pass,” Laszewski told Medscape Medical News.

He said that Warren’s proposals would amount to an average 22% reduction in pay for most physicians, with some specialties seeing an even bigger pay cut. Hospital reimbursement would be cut in half, he said.

Warren’s proposals would amount to an average 22% reduction in pay for most physicians, with some specialties seeing an even bigger pay cut.

Less Overhead = Better Pay?

Warren said her plan would reduce administrative spending and waste. Private insurers spend 12% of premiums on administration, while that figure is 2.3% for Medicare, she said, using that number as her plan’s benchmark to set net administrative spending.

“The improved efficiency will save doctors time and money — helping significantly offset the revenue they will lose from getting rid of higher private insurance rates,” Warren said.

Laszewski doesn’t buy it. “There’s as much hassle for doctors in Medicare as there is in private insurance,” he said.

Warren also promised to increase reimbursement for primary care physicians, while cutting pay for what she called “overpaid specialties,” as defined by a Medicare Prospective Payment Assessment Commission report done for the Medicare Payment Advisory Commission in January 2019.

In addition, Medicaid reimbursement would be raised to Medicare pay rates.

Big Blow for Hospitals

Warren is proposing to pay hospitals an average of 110% of current Medicare rates, with adjustments for rural hospitals, teaching hospitals, and others “with challenging cost structures,” according to the plan.

She contends that will cover current costs of care, and that hospitals will see a reduction in costs because of simpler administrative processes, lower drug prices, the elimination of uncompensated care, and a higher volume of patients.

Laszewski, however, notes that without private insurance, hospitals will be losing a higher rate of pay that accounts for 60% of their business. “They’re not going to get more, they’re going to get a hell of a lot less,” he said.

Warren is also proposing to strictly regulate consolidation among hospitals, contending that bigger entities are anticompetitive. “I will direct my [Federal Trade Commission] to block all future hospital mergers unless the merging companies can prove that the newly-merged entity will maintain or improve care,” she said in her plan.

The American Hospital Association (AHA) expressed concern. “Hospitals are already paid far less than the cost of caring for Medicare patients — and patients on an underfunded system would strain hospitals even more — and could threaten access to care and hospitals’ survival,” said Tom Nickels, AHA executive vice president.

“Further, the government can be an unreliable business partner and has a history of using provider payments for other programs to meet its budgetary goals,” he said, in a statement emailed to Medscape Medical News.

“The AHA believes there is a better alternative to help all Americans access health coverage — one built on improving our existing system rather than ripping it apart and starting from scratch,” he said.

When asked for comment, the American Medical Association noted that it does not support or endorse presidential candidates, and thus does not comment on candidates’ proposals.

https://www.medscape.com/viewarticle/920768#vp_1

‘No Identifiable Reason’ for 50% of Antipsychotic Use in ADHD

Only about 50% of antipsychotic prescriptions for children and youth who have been newly diagnosed with attention-deficit/hyperactivity disorder (ADHD) have an identifiable clinical indication. Furthermore, fewer than half of these patients receive initial treatment with stimulants ― the recommended first-line pharmacologic therapy ― results of a national analysis show.

Dr Ryan S. Sultan

“Overall, we found that 2.6% of kids with a new diagnosis of ADHD were treated with an antipsychotic medication despite no FDA [US Food and Drug Administration–approved] indication,” study investigator Ryan S. Sultan, MD, assistant professor of clinical psychiatry, Columbia University, New York City, told Medscape Medical News.

“Among these, 52.7% had a potential clinical explanation for the administration of an antipsychotic, such as evidence of treatment-resistant ADHD. That still leaves approximately half of them who have no identifiable reason for receiving an antipsychotic. But they did nonetheless,” he added.

The findings were presented here at the American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting.

Increased Risk for Death

There is significant concern over the use of antipsychotics to treat ADHD in children and youth. Nevertheless, during the past decade, the prescribing of these agents in this population has increased by 50%.

Although some of this rise may be attributable to prescribing for clinical indications approved by the FDA, including schizophrenia, bipolar disorder, irritability associated with autism spectrum disorder, and Tourette syndrome, much of it is associated with off-label prescribing for ADHD. Sultan noted there’s not much known about the factors driving antipsychotic prescribing in this population.

The investigators also note that antipsychotic prescribing in youth is associated with adverse metabolic effects, including rapid weight gain, hyperlipidemia, and increased risk for type 2 diabetes. More recently, as reported by Medscape Medical News, antipsychotics have been linked to an increased risk for unexpected death in this patient population.

“There’s been a lot of discussion about poor pharmacologic treatment in children and youth with ADHD. We were concerned. Why is such a significant proportion of children getting an antipsychotic? So we wanted to do a deeper dive,” said Sultan.

To determine the percentage of youth for whom antipsychotic prescriptions were filled in the year following an initial diagnosis of ADHD, the investigators examined clinical and demographic factors associated with antipsychotic prescribing in children and youth with ADHD.

With coinvestigator Mark Olfson, MD, MPH, Sultan obtained data from the Truven Health MarketScan Commercial Database for January 1, 2010, to December 31, 2015. This database includes a host of medical and prescription drug data for more than 110 million patients.

The retrospective, longitudinal cohort analysis included 187,563 children and youth (aged 3 years to 24 years) who were newly diagnosed with ADHD but who did not have FDA-approved or evidence-based indications for antipsychotic treatment.

The researchers examined several outcome measures, including the percentage of patients who were prescribed an antipsychotic in the first year following a new diagnosis of ADHD and the percentage for whom an antipsychotic prescription was filled before a prescription for a stimulant was filled.

“Deeply Concerning”

They also examined a subset of youth who were prescribed antipsychotic medications. They assessed the percentage of those who received a diagnosis of conduct disorder, oppositional defiant disorder, or a disorder that was an FDA-approved indication with respect to at least one antipsychotic medication.

The mean age of the children and youth included in the study was 13.74 ± 5.61 years; 114,305 (60.9%) were male. The investigators found that within 1 year of their being newly diagnosed with ADHD, antipsychotics were initiated in 4869 patients (2.6%; 95% confidence interval [CI], 2.5% – 2.7%).

The investigators found that there was a potential clinical diagnostic rationale for treatment with antipsychotic medications for only 52.7% of patients who received them.

“I would understand these results if these children had complicated cases with aggression, and the stimulant was tried and didn’t work. But that was not the case, because half of the antipsychotic-treated youth with ADHD never got a stimulant medication before they got an antipsychotic. It’s deeply concerning. These youth have no clear indication for an antipsychotic, and stimulants are bread-and-butter treatment for ADHD,” said Sultan.

“Assuming they aren’t very young or only have mild symptoms, the treatment recommendations for ADHD are that you give adequate treatment trials for each psychostimulant class first; you don’t jump right to an antipsychotic,” he said.

Patients who received antipsychotics were more likely to be male, to be aged 13 to 18 years, to have been recently diagnosed with comorbid mental health conditions, or to have recently been admitted for inpatient mental health treatment.

Antipsychotic initiation was associated with self-harm or suicidal ideation (adjusted odds ratio [aOR], 7.5; 95% CI, 5.9 – 9.6), oppositional defiant disorder diagnosis (aOR, 4.4; 95% CI, 3.9 – 4.9), substance use disorder (aOR, 4.0; 95% CI, 3.6 – 4.5), and inpatient mental health care (aOR, 7.9; 95% CI, 6.7 – 9.3) in the preceding 6 months.

The analysis also showed that initial treatment with stimulants was not as common among ADHD patients who received antipsychotics. Indeed, 47.9% (95% CI, 46.5% – 49.3%) received no initial stimulant therapy before initiation of antipsychotics.

Similarly, 43.8% (95% CI, 42.4% – 45.1%) received a drug of one stimulant class, and only 8.4% of patients (95% CI, 7.6% – 9.1%) received methylphenidate or a methylphenidate derivative and an amphetamine derivative.

Going forward, the investigators plan to use electronic health and medical records to further analyze the findings in order to identify the specific reasons young patients were initially treated with antipsychotics.

“Is it that the parent refused the stimulant and now the child is in the emergency room with severe aggressive behavior and someone has reactively started giving an antipsychotic?”

“Major Tranquilizers”

Commenting on the findings for Medscape Medical News, Lily Hechtman, MD, McGill University, Montreal, Canada, noted that antipsychotics have traditionally been prescribed for children with ADHD with comorbid aggression.

“However, these types of medications also have many serious side effects, and it is generally believed that a comprehensive behavioral approach for parents and the child is best to treat these children. More recently, guanfacine ― which is not an antipsychotic and has fewer negative side effects ― has been shown to be effective for aggressive outbursts,” she said.

“Antipsychotics are really major tranquilizers,” Hechtman added, “so it’s important not to assume that we are dealing with a psychotic process when we are really just observing a tranquilizing effect. Children with ADHD have many comorbidities, but psychosis is really very rare.”

Sultan recognized that antipsychotic therapy does play a role in ADHD treatment for a small subset of children and youth.

“I’ll be the first to admit that there may be occasions where antipsychotics may be the right thing to do,” he explained. “But for me, that’s only after you’ve used two stimulants, have done behavioral training and parent-management training, and still have severe symptoms. Alternatively, they can be prescribed on a short-term basis if there is evidence of aggression causing acute danger. But they should not be first line, which is essentially what this analysis suggests.”

The study was funded by an AACAP Pilot Research Award for Attention Disorders. Sultan and Hechtman have disclosed no relevant financial relationships.

American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting: Abstract 2.3, presented October 16, 2019.

https://www.medscape.com/viewarticle/920777#vp_1

Cervical pre-cancer can be detected in self-collected urine or vaginal samples

Researchers have developed a non-invasive test to detect cervical pre-cancer by analysing urine and vaginal samples collected by the women themselves.

In a presentation at the 2019 NCRI Cancer Conference today (Monday), Dr. Belinda Nedjai said that self-sampling test had proved popular with women taking part in the study and this meant that it was likely to improve participation in cervical cancer screening programmes.

“The initial use of self-sampling is likely to be for women who do not attend clinic after a screening invitation and countries without a cervical cancer screening programme. In the longer term, self-sampling could become the standard method for all screening tests. The study indicated that women much preferred doing a test at home than attending a doctor’s surgery,” said Dr. Nedjai, who is Senior Research Fellow and Director of the Molecular Epidemiology Lab at Queen Mary University of London, UK.

“To the best of our knowledge, this study is the largest to test a methylation classifier, called S5, in urine and self-collected cervical samples to detect pre-cancer lesions in women who have been referred for further investigation. We expect the self-sampling test to improve acceptance rates for cervical cancer screening, as well as reducing costs to health services and improving the performance of screening programmes.”

The current gold-standard pap smear test is taken in the clinic and often follows a positive test for the human papilloma virus (HPV).

Dr. Nedjai said: “HPV testing is rapidly becoming the primary screening method for cervical cancer worldwide. It is a very sensitive method, very good at detecting true positives, but lacks specificity—in other words, a second test is needed to exclude HPV positive women that are not at increased risk of developing cancer. The choice of an appropriate strategy for high-risk HPV positive women is a key issue.”

The S5 test developed by Dr. Nedjai and her colleagues at Queen Mary, measures DNA methylation—a chemical change to one of the four DNA base letters that make up the human genetic code. S5 looks at DNA methylation of four HPV types most strongly associated with cancer—HPV16, HPV18, HPV31 and HPV33—and the human gene EPB41L3 to produce a score that indicates the level of risk. If the score is above a selected cut-off it indicates an increased risk of a pre-cancer lesion, and the higher the score the higher the risk of cancer. They had discovered in earlier research that when S5 was used on cervical samples, it was 100% accurate at detecting invasive cervical cancer, and 93% accurate at detecting pre-cancer in women who had an HPV positive test.

Cervical cancer is preceded by the abnormal growth of precursor cells on the surface of the cervix—so called cervical intraepithelial neoplasia (CIN) or pre-cancer—that can develop into cervical cancer. It is divided into three stages (CIN1, CIN2 and CIN3), with the likelihood of the cells developing into cancer increasing at each stage.

“We decided to assess whether S5 could identify women who had CIN3 pre-cancer lesions using urine and vaginal samples,” said Dr. Nedjai.

Women attending the colposcopy clinic at the Royal London Hospital as a consequence of an abnormal smear test or positive HPV result were asked to take part in a study led by Professor Jack Cuzick, Director of the Wolfson Institute of Preventive Medicine at Queen Mary. A total of 620 women provided vaginal samples, collected themselves using vaginal swabs, and 503 of these women also provided a urine sample. The researchers extracted and analysed the DNA in the lab and generated S5 scores.

“We found that S5 classifier with or without HPV testing worked well in both urine and vaginal samples,” said Dr. Nedjai. “It distinguished between women who had no pre-cancerous lesions and those who had CIN3 or higher lesions. We evaluated two distinct ways that S5 could be used. We first tested S5 as a secondary test on HPV positive women to limit the number of patients sent to colposcopy. In urine, S5 was better at correctly identifying women who did have pre-cancer lesions than testing for the presence of HPV16 or 18; 96% of true CIN3 were identified with S5 compared to 73% with an HPV16 or 18 test. Secondly, we evaluated S5 as a standalone test, without first doing HPV testing. We adjusted the cut-offs to identify at least 85% of true positives. Urine performed as well as self-collected vaginal samples.

“We are currently working on new markers to try to improve the accuracy of the classifier even further, but these findings represent an advance in cervical cancer screening, especially for women who do not attend the clinic, such as older women, or women who find the smear test too painful or who do not have access to a screening programme in their country. We think it’s promising.”

In the future, Dr. Nedjai said the samples could be collected at home for both HPV and methylation analysis without the need to go to the clinic.

Dr. Manuel Rodriguez-Justo is a consultant pathologist at University College London (UK) and a member of the NCRI’s sub-committee on early detection and prevention. He was not involved with the research. He commented: “This is exciting research that shows it’s possible to detect cervical pre-cancer that is at high risk of developing into invasive cancer in urine and vaginal samples collected by women in the comfort and privacy of their own homes. This has the potential to revolutionise the way a positive HPV test is followed up, as well as making it easier for women in countries with no cervical cancer screening programme to be tested.

“The cervical screening programme in the UK has been very successful but there has been also a decline in its uptake, particularly in some areas in the UK and specific ethnic groups. If the results of this study are validated by other groups, the implementation of urine-based testing and self-sampled vaginal samples will, potentially, increase uptake and reduce costs for the screening programmes whilst achieving high sensitivity to detect pre-malignant lesions

Cervical cancer is the fourth most frequently occurring cancer in women in the world. In 2018, there were an estimated 570,000 new cases of cervical cancer and 310,000 women died from the disease. Infection with HPV is almost the main cause of cervical cancer. More than 25 different types of HPV are transmitted through sexual contact and 12 of them carry a high risk of triggering the development of cancer cells by inactivating tumour suppressor proteins (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 68).

Explore further

Urine test could prevent cervical cancer

More information: Abstract no: Poster 2451, poster board number 43, area 2. “Non-invasive methylation test to detect cervical pre-cancer in self-collected vaginal and urine specimens”, by Belinda Nedjai. 15.47 hrs GMT. Silent theatre 2, Exhibition Hall, Monday 4 November.

https://medicalxpress.com/news/2019-11-cervical-pre-cancer-self-collected-urine-vaginal.html

1 in 3 young adults get meds for opioid use disorder after overdose

One in three young adults receive medication for opioid use disorder in the 12 months after surviving an overdose, according to a study published online Oct. 4 in the Annals of Emergency Medicine.

Sarah M. Bagley, M.D., from Boston University, and colleagues used administrative data to identify 15,281 individuals aged 18 to 45 years who survived an opioid-related overdose in Massachusetts between 2012 and 2014. Characteristics of young adults were assessed and rates of medication for opioid use disorder were compared for adults aged 18 to 25 versus 26 to 45 years.

The researchers found that 28 percent of patients aged 18 to 21 years, 36 percent of those aged 22 to 25 years, and 36 percent of those aged 26 to 45 years received treatment. For individuals aged 18 to 25 years, median time to buprenorphine treatment was four months compared with four months to methadone treatment and one month to naltrexone treatment. Compared with those aged 22 to 25 and 26 to 45 years, individuals aged 18 to 21 years were less likely to receive methadone (adjusted hazard ratio, 0.60). Compared with those aged 26 to 45 years, individuals aged 18 to 21 years and those aged 22 to 25 years were more likely to receive naltrexone (adjusted hazard ratios, 1.65 and 1.41, respectively).

“These results indicate that age appears to be a factor in the type of medication administered to treat opioid use disorder,” Bagley said in a statement. “It is important that young adults who survive an overdose have access to medication, including when they are treated in the emergency department or in the hospital or outpatient settings. All of these encounters are critical opportunities to engage them in treatment, which can save their life.”

Explore further

One in three young adults receive medication for opioid use disorder after overdose

More information: Abstract/Full Text (subscription or payment may be required)

https://medicalxpress.com/news/2019-11-young-adults-meds-opioid-disorder.html