Prenatal opioid exposure could bring long-term harm to children, study says

Prenatal Risk Factors and Perinatal and Postnatal Outcomes Associated With Maternal Opioid Exposure in an Urban, Low-Income, Multiethnic US Population

According to a new study, children exposed to opioids in the womb may have heightened risks of long-term mental and physical health issues, medicalxpress reports.

Key Points

Question
What are the prenatal risk factors and perinatal and postnatal outcomes associated with maternal opioid use during pregnancy?

Findings
In this cohort study based on data from 8509 mother-child pairs in the Boston Birth Cohort, in utero opioid exposure was significantly associated with higher risks of fetal growth restriction, preterm birth, lack of expected physiological development, childhood conduct disorder or emotional disturbance in preschool-aged children, and attention-deficit/hyperactivity disorder in school-aged children.

Meaning
Prenatal opioid exposure was associated with higher risks of adverse perinatal and postnatal physical health and neurodevelopmental outcomes, suggesting that efforts to mitigate the health consequences of the opioid epidemic require more intergenerational research.

2019 Study Abstract

Importance
The opioid epidemic increasingly affects pregnant women and developing fetuses, resulting in high rates of neonatal abstinence syndrome. However, longitudinal studies that prospectively observe newborns with neonatal abstinence syndrome or with maternal opioid use and examine their long-term physical and neurodevelopmental outcomes are lacking.

Objective
To examine prenatal risk factors associated with maternal opioid use during pregnancy and the short-term and long-term health consequences on their children.

Design, Setting, and Participants
This cohort study analyzed data from the Boston Birth Cohort, an urban, low-income, multiethnic cohort that enrolled mother-newborn pairs at birth at Boston Medical Center (Boston, Massachusetts) starting in 1998, and a subset of children were prospectively observed at Boston Medical Center pediatric primary care and subspecialty clinics from birth to age 21 years. Data analysis began in June 2018 and was completed in May 2019.

Exposures
In utero opioid exposure was defined as maternal self-reported opioid use and/or clinical diagnosis of neonatal abstinence syndrome.

Main Outcomes and Measures
Pregnancy outcomes, postnatal child physical health, and major neurodevelopmental disabilities, documented in maternal and child medical records.

Results
This study included 8509 Boston Birth Cohort mother-newborn pairs for prenatal and perinatal analyses. Of those, 3153 children continued to receive pediatric care at Boston Medical Center and were included in assessing postnatal outcomes. Overall, 454 of the 8509 children (5.3%) in the Boston Birth Cohort had in utero opioid exposure. At birth, opioid exposure was associated with higher risks of fetal growth restriction (odds ratio [OR], 1.87; 95% CI, 1.41-2.47) and preterm birth (OR, 1.49; 95% CI, 1.19-1.86). Opioid exposure was associated with increased risks of lack of expected physiological development (OR, 1.80; 95% CI, 1.17-2.79) and conduct disorder/emotional disturbance (OR, 2.13; 95% CI, 1.20-3.77) among preschool-aged children. In school-aged children, opioid exposure was associated with a higher risk of attention-deficit/hyperactivity disorder (OR, 2.55; 95% CI, 1.42-4.57).

Conclusions and Relevance
In this sample of urban, high-risk, low-income mother-child pairs, in utero opioid exposure was significantly associated with adverse short-term and long-term outcomes across developmental stages, including higher rates of physical and neurodevelopmental disorders in affected children. Efforts to prevent the opioid epidemic and mitigate its health consequences would benefit from more intergenerational research.

Pharma sales rep paid physicians to participate in hundreds of sham “speaker programs” in order to prescribe med drugs

Subsys : Drug Company Sales Rep Sentenced for Role in Kickback Scheme Related to Fentanyl Spray Prescriptions

John H. Durham, United States Attorney for the District of Connecticut, announced that NATALIE LEVINE, 35, of Scottsdale, Arizona, was sentenced today by U.S. District Judge Janet Bond Arterton in New Haven to five years of probation for engaging in a kickback scheme related to fentanyl spray prescriptions. Judge Arterton also ordered Levine to spend the first six months of probation in home confinement, and to perform 150 hours of community service.

According to court documents and statements made in court, from approximately March 2013 to October 2014, Levine was employed by Insys Therapeutics, an Arizona-based pharmaceutical company that manufactured and sold Subsys, a fentanyl-based sublingual spray that was approved by the Food and Drug Administration solely for the management of breakthrough pain in cancer patients. Levine was a sales representative for the company and was responsible for covering the territories that included Connecticut, New Hampshire and Rhode Island.

Levine induced certain medical practitioners, including an advanced practice registered nurse (APRN) in Connecticut, a physician’s assistant (PA) in New Hampshire, and a physician in Rhode Island, to prescribe Subsys by paying them to participate in hundreds of sham “Speaker Programs.” The Speaker Programs, which were typically held at high-end restaurants, were ostensibly designed to gather licensed healthcare professionals who had the capacity to prescribe Subsys and educate them about the drug. In truth, the events were usually just a gathering of friends and co-workers, most of whom did not have the ability to prescribe Subsys, and no educational component took place. “Speakers” were paid a fee that ranged from $1,000 to several thousand dollars for attending these dinners. At times, the sign-in sheets for the Speaker Programs were forged so as to make it appear that the programs had an appropriate audience of healthcare professionals.

The medical practitioners were paid thousands of dollars in illegal kickbacks in order to prescribe Subsys, and induce others to prescribe Subsys, over similar medications. Medicare Part D plans authorized payment for hundreds of Subsys prescriptions written by the three medical practitioners, resulting in a loss of approximately $4.5 million.

Levine’s restitution figure will be determined after additional court proceedings.

On July 11, 2017, Levine pleaded guilty to one count of conspiracy to violate the anti-kickback law.

Several other individuals affiliated with Insys Therapeutics, and medical practitioners involved in this kickback scheme, have been charged and convicted in the District of Connecticut and in other Districts across the United States. In sentencing Levine, Judge Arterton credited Levine’s significant cooperation and assistance to the government’s prosecution of defendants in Connecticut, Massachusetts, New Hampshire and Rhode Island.

On January 3, 2019, Levine’s husband, Michael Babich, who was the CEO and President of Insys Therapeutics, pleaded guilty in the District of Massachusetts to conspiracy and fraud charges stemming from the scheme. He awaits sentencing.

On May 2, 2019, a federal jury in Boston found John N. Kapoor, the founder and former Executive Chairman of Insys Therapeutics, and four other former Insys executives guilty of racketeering conspiracy.

Earlier this month, Insys Therapeutics agreed to pay a total of $225 million to resolve criminal and civil investigations of the company.

The investigation in the District of Connecticut is being conducted by the U.S. Department of Health and Human Services Office of the Inspector General and the Federal Bureau of Investigation, with the assistance of the Drug Enforcement Administration’s Tactical Diversion Squad. The case is being prosecuted by Assistant U.S. Attorneys Douglas P. Morabito, Sarah P. Karwan and Richard M. Molot.

U.S. Attorney Durham encouraged individuals who suspect health care fraud to report it by calling the Health Care Fraud Task Force (203) 785-9270 or 1-800-HHS-TIPS.

Department of Justice
U.S. Attorney’s Office, District of Connecticut, News And Press Releases, Monday June 24, 2019

Chronic use of tramadol after acute pain episode: cohort study

Tramadol use is associated with a higher risk of prolonged opioid use in patients with an acute episode of pain compared with other short acting opioids, finds new research

2019 Study Abstract

Objective
To determine the risk of prolonged opioid use in patients receiving tramadol compared with other short acting opioids.

Design
Observational study of administrative claims data.

Setting
United States commercial and Medicare Advantage insurance claims (OptumLabs Data Warehouse) January 1, 2009 through June 30, 2018.

Participants
Opioid-naive patients undergoing elective surgery.

Main outcome measure
Risk of persistent opioid use after discharge for patients treated with tramadol alone compared with other short acting opioids, using three commonly used definitions of prolonged opioid use from the literature: additional opioid use (defined as at least one opioid fill 90-180 days after surgery); persistent opioid use (any span of opioid use starting in the 180 days after surgery and lasting ≥90 days); and CONSORT definition (an opioid use episode starting in the 180 days after surgery that spans ≥90 days and includes either ≥10 opioid fills or ≥120 days’ supply of opioids).

Results
Of 444 764 patients who met the inclusion criteria, 357 884 filled a discharge prescription for one or more opioids associated with one of 20 included operations. The most commonly prescribed post-surgery opioid was hydrocodone (53.0% of those filling a single opioid), followed by short acting oxycodone (37.5%) and tramadol (4.0%). The unadjusted risk of prolonged opioid use after surgery was 7.1% (n=31 431) with additional opioid use, 1.0% (n=4457) with persistent opioid use, and 0.5% (n=2027) meeting the CONSORT definition. Receipt of tramadol alone was associated with a 6% increase in the risk of additional opioid use relative to people receiving other short acting opioids (incidence rate ratio 95% confidence interval 1.00 to 1.13; risk difference 0.5 percentage points; P=0.049), 47% increase in the adjusted risk of persistent opioid use (1.25 to 1.69; 0.5 percentage points; P<0.001), and 41% increase in the adjusted risk of a CONSORT chronic opioid use episode (1.08 to 1.75; 0.2 percentage points; P=0.013).

Conclusions
People receiving tramadol alone after surgery had similar to somewhat higher risks of prolonged opioid use compared with those receiving other short acting opioids. Federal governing bodies should consider reclassifying tramadol, and providers should use as much caution when prescribing tramadol in the setting of acute pain as for other short acting opioids.

Pharma industry marketing linked to increased prescribing and elevated mortality

Association of Pharmaceutical Industry Marketing of Opioid Products With Mortality From Opioid-Related Overdoses

The new study concluded that drug companies’ marketing of opioids to physicians was “associated with increased opioid prescribing and, subsequently, with elevated mortality from overdoses.”

Read Opioid crisis shows partnering with industry can be bad for public health, theconversation, March 6, 2019.

2019 Study Key Points

Question
To what extent is pharmaceutical industry marketing of opioids to physicians associated with subsequent mortality from prescription opioid overdoses?

Findings
In this population-based, cross-sectional study, $39.7 million in opioid marketing was targeted to 67 507 physicians across 2208 US counties between August 1, 2013, and December 31, 2015. Increased county-level opioid marketing was associated with elevated overdose mortality 1 year later, an association mediated by opioid prescribing rates; per capita, the number of marketing interactions with physicians demonstrated a stronger association with mortality than the dollar value of marketing.

Meaning
The potential role of pharmaceutical industry marketing in contributing to opioid prescribing and mortality from overdoses merits ongoing examination.

Abstract

Importance
Prescription opioids are involved in 40% of all deaths from opioid overdose in the United States and are commonly the first opioids encountered by individuals with opioid use disorder. It is unclear whether the pharmaceutical industry marketing of opioids to physicians is associated with mortality from overdoses.

Objective
To identify the association between direct-to-physician marketing of opioid products by pharmaceutical companies and mortality from prescription opioid overdoses across US counties.

Design, Setting, and Participants
This population-based, county-level analysis of industry marketing information used data from the Centers for Medicare & Medicaid Services Open Payments database linked with data from the Centers for Disease Control and Prevention on opioid prescribing and mortality from overdoses. All US counties were included, with data on overdoses from August 1, 2014, to December 31, 2016, linked to marketing data from August 1, 2013, to December 31, 2015, using a 1-year lag. Statistical analyses were conducted between February 1 and June 1, 2018.

Main Outcomes and Measures
County-level mortality from prescription opioid overdoses, total cost of marketing of opioid products to physicians, number of marketing interactions, opioid prescribing rates, and sociodemographic factors.

Results
Between August 1, 2013, and December 31, 2015, there were 434 754 payments totaling $39.7 million in nonresearch-based opioid marketing distributed to 67 507 physicians across 2208 US counties. After adjustment for county-level sociodemographic factors, mortality from opioid overdoses increased with each 1-SD increase in marketing value in dollars per capita (adjusted relative risk, 1.09; 95% CI, 1.05-1.12), number of payments to physicians per capita (adjusted relative risk, 1.18; 95% CI, 1.14-1.21, and number of physicians receiving marketing per capita (adjusted relative risk, 1.12; 95% CI, 1.08-1.16). Opioid prescribing rates also increased with marketing and partially mediated the association between marketing and mortality.

Conclusions and Relevance
In this study, across US counties, marketing of opioid products to physicians was associated with increased opioid prescribing and, subsequently, with elevated mortality from overdoses. Amid a national opioid overdose crisis, reexamining the influence of the pharmaceutical industry may be warranted.

Les USA, pays accro aux opioïdes

L’INSTANT M, Jeudi 21 février 2019, par Sonia Devillers

Le journaliste Pierre Monégier a enquêté sur les ravages d’un médicament antidouleur, qui provoque la mort sur ordonnance à tous les coins de rue.

En Savoir Plus

Opioïdes : l’Amérique dévastée

Enquête sur un pays accro aux médicaments antidouleurs

Un couple de personnes âgées inanimées sur un banc en pleine rue, une petite fille en pleurs devant sa maman qui a perdu conscience dans les rayons d’un supermarché : un type de vidéos chocs semble-t-il de plus en plus nombreuses.

Les opioïdes ont inondé le marché américain.

Tout commence souvent par un mal de dos, une douleur chronique ou des rhumatismes : leur médecin prescrit des opioïdes…

“Envoyé spécial” diffuse un document exceptionnel dans une Amérique en pleine overdose.

Référence 1. Référence 2. Référence 3. Référence 4.

Un reportage de Pierre Monégier, Brice Baubit et Emmanuel Lejeune,

Addiction sur ordonnance

Médicaments opioïdes : première cause de mort par overdose en France

Les opioïdes tuent aussi en France : ils sont devenus la première cause de mort par overdose : trois décès par jour, un millier chaque année.

Il y a désormais plus d’overdoses chez les patients souffrant de douleurs chroniques que chez les toxicomanes.

Référence 1. Référence 2.

État des lieux de la consommation des antalgiques opioïdes et leurs usages problématiques

Antalgiques opioïdes : l’ANSM publie un point d’Information février 2019

La prévention des risques liés aux antalgiques opioïdes est une préoccupation majeure des autorités de santé. L’Agnce nationale de sécurité du médicament et des produits de santé (ANSM) publie un rapport sur la consommation des antalgiques opioïdes en France, s’inscrivant ainsi dans une démarche de surveillance globale de l’utilisation des médicaments utilisés dans la prise en charge de la douleur.

En 10 ans, la consommation des antalgiques opioïdes a augmenté ; cela s’inscrit dans la politique d’amélioration de la prise en charge de la douleur de part, notamment, des plans ministériels de lutte contre la douleur ayant été mis en place depuis 1998.

En parallèle, l’ANSM observe une augmentation du mésusage, ainsi que des intoxications et des décès liés à l’utilisation des antalgiques opioïdes, qu’ils soient faibles ou forts. Cependant, la situation n’est pas comparable avec celle observée aux Etats-Unis et au Canada.

L’enjeu pour les autorités sanitaires françaises consiste à sécuriser au mieux l’utilisation des antalgiques opioïdes sans restreindre leur accès aux patients qui en ont besoin.

En France, l’ANSM mène régulièrement des actions visant à contrôler l’encadrement de ces médicaments en termes de conditions de prescription et de délivrance, d’interdiction de publicité auprès du grand public, d’informations à destination des professionnels de santé. Elle surveille attentivement la consommation des antalgiques opioïdes et des risques associés.

Les principaux enseignements du rapport :

  • D’après les données de l’assurance maladie, près de 10 millions de français ont eu une prescription d’antalgique opioïde en 2015. En 2017, l’antalgique opioïde le plus consommé en France est le tramadol puis la codéine en association et la poudre d’opium associée au paracétamol. Viennent ensuite la morphine, premier antalgique opioïde fort, l’oxycodone, à présent pratiquement autant consommé que la morphine, puis le fentanyl transdermique et transmuqueux à action rapide.
  • Entre 2006 et 2017, la prescription d’opioïdes forts a augmenté d’environ 150 %[3] . L’oxycodone est l’antalgique opioïde qui marque l’augmentation la plus importante.
  • La consommation globale des opioïdes faibles est restée relativement stable. Le retrait du dextropropoxyphène en 2011 a été accompagné de l’augmentation de la consommation des autres opioïdes faibles et en particulier du tramadol. Il devient l’antalgique opioïde le plus consommé (forts et faibles confondus) avec une augmentation de plus de 68 % entre 2006 et 2017.
  • Les opioïdes ont un intérêt majeur et incontestable dans la prise en charge de la douleur et restent moins consommés que les antalgiques non-opioïdes (paracétamol, aspirine, AINS). Cependant, la consommation des antalgiques opioïdes peut s’accompagner de complications graves. Cette problématique touche principalement des patients qui consomment un antalgique opioïde pour soulager une douleur, et qui développent une dépendance primaire à leur traitement, et parfois le détournent de son indication initiale. Ainsi, le nombre d’hospitalisations liées à la consommation d’antalgiques opioïdes obtenus sur prescription médicale a augmenté de 167 % entre 2000 et 2017 passant de 15 à 40 hospitalisations pour un million d’habitants. Le nombre de décès liés à la consommation d’opioïdes a augmenté de 146 %, entre 2000 et 2015, avec au moins 4 décès par semaine.

Référence.

Doctors’ unconscious instinct to reciprocate med reps’ gifts

What Big Pharma knows about people’s hardwired instinct to return the favor when given a gift

Abstract

… “You might reasonably ask whether a modest meal with a pharmaceutical sales rep matters all that much. You might also be surprised by what a small gift can buy. In recent years, social psychologists and marketers have demonstrated that the pull of reciprocity is exceedingly powerful in human beings, often acting on us in ways we may not consciously appreciate. Perhaps it’s too much to suggest that free pens were responsible for the opioid epidemic. But it’s become more and more clear that a gift, even from a salesperson, can make the receiver feel obliged to give something in return.” …

Read Did Free Pens Cause the Opioid Crisis? on the atlantic, about the role of medical representatives in the promotion of pharmaceuticals in general, and the opioid crisis in particular.