Tobacco smoking rates are decreasing in people with major depression and substance use disorder

Significant reductions in cigarette use were found among U.S. adults with major depression, substance use disorder, or both from 2006 to 2019, according to a new analysis of nationally representative survey data published today in JAMA. 

Smoking is a modifiable risk factor for cardiovascular disease and 73% of African American adults who smoke want to quit,

The study was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Substance Abuse and Mental Health Services Administration (SAMHSA).

These findings suggest that groups at higher risk of cigarette smoking can be reached by, and may have benefitted from, tobacco use prevention and cessation efforts that have led to significant declines in tobacco use in the general population. At the same time, the findings highlight remaining disparities, documenting higher smoking rates in people with psychiatric disorders than in those without.

“This study shows us that, at a population-level, reductions in tobacco use are achievable for people with psychiatric conditions, and smoking cessation should be prioritized along with treatments for substance use, depression, and other mental health disorders for people who experience them,” said Nora Volkow, M.D., director of NIDA and co-author of the study. “Therapies to help people stop smoking are safe, effective, and may even enhance the long-term success of concurrent treatments for more severe mental health symptoms in individuals with psychiatric disorders by lowering stress, anxiety, depression, and by improving overall mood and quality of life.”

Cigarette smoking, the leading preventable cause of disease, disability and death in the U.S., has been declining. Experts attribute this in part to increases in available treatments, insurance coverage of these treatments, cigarette prices, smoke-free and tobacco-free policies, mass media and educational campaigns and other evidence-based strategies to help people avoid or quit using cigarettes that have been implemented in recent decades.

Quitting cigarette smoking and tobacco use reduces the risk of cancer, heart disease, stroke and lung diseases. Studies have also found that smoking cessation in people with psychiatric disorders can help decrease anxiety, depression and stress; lower likelihood of a new-onset substance use disorder; and improve quality of life.

Past studies have documented that smoking rates remained essentially unchanged in people with substance use disorders, major depression or other psychiatric disorders. Now, analyzing data from more than 558,000 individuals aged 18 and older who participated in the 2006 to 2019 National Surveys on Drug Use and Health (NSDUH), researchers found that while people with major depression, substance use disorder or both were more likely to smoke cigarettes than people without these disorders; improvements in smoking cessation were seen among those with these psychiatric disorders during the 14-year period. The NSDUH, conducted annually by SAMHSA, provides nationally representative data on cigarette smoking, tobacco use, major depressive episode and substance (alcohol or drug) use disorders among the US civilian, non-institutionalized adult population. Among the population studied here, roughly 53% were women, 41% were aged 18 to 25 and 62% were non-Hispanic white.

After controlling for factors such as age, sex, race/ethnicity, education and family income, the researchers found that past-month smoking rates declined by 13.1% from 2006 to 2019 among adults with a past-year major depressive episode and by 8.2% from 2006 to 2019 among adults without. The difference in past-month cigarette smoking among those with versus without past-year major depressive episode significantly narrowed from 11.5% in 2006 to 6.6% in 2019.

Similarly, past-month cigarette smoking declined by 10.9% from 2006 to 2019 among adults with past-year substance use disorder and by 7.8% among adults without. For people with co-occurring substance use disorder and major depression, past-month smoking rates decreased by 13.7% during this 14-year period and by 7.6% among adults without these disorders.

“These declines tell a public health success story,” said Wilson Compton, M.D., NIDA’s Deputy Director and the senior author of the study. “However, there’s still a lot of work to be done to ensure tobacco use in patients with substance use disorder, depression, or other psychiatric conditions continue to decrease. It is crucial that healthcare providers treat all the health issues that a patient experiences, not just their depression or drug use disorder at a given point in time. To do this, smoking cessation therapies need to be integrated into existing behavioral health treatments. The result will be longer and healthier lives for all people.”

During 2006 to 2019, among adults with past-year major depressive episodes or substance use disorder, past-month cigarette smoking declined significantly across every examined age, sex, and racial and ethnic subgroup, except that among non-Hispanic American Indian or Alaska Native adults smoking rates did not decline. Given that American Indian and Alaska Native communities face the highest smoking and lowest quitting rates among racial and ethnic subgroups in the United States, this highlights the need to channel additional prevention and treatment efforts into these communities.

In future work, the researchers note the need to include data on certain populations at high risk of psychiatric disorders and cigarette smoking, such as institutionalized individuals or those experiencing homelessness without living in a shelter. More work is also needed to continue to monitor national trends in differences in tobacco use and nicotine vaping among adults with or without psychiatric conditions – including substance use disorder – during the COVID-19 pandemic.

Central African Republic: War Crimes Court’s First Trial

The opening of the first trial at the Central African Republic’s Special Criminal Court (SCC) on April 19, 2022 represents significant progress in the difficult effort to see justice for grave crimes committed in the country, Human Rights Watch said today. Human Rights Watch issued a question-and-answer document ahead of the SCC’s trial. 

The case involves war crimes and crimes against humanity committed in May 2019 in Koundjili and Lemouna allegedly by the suspects, Issa Sallet Adoum, Ousman Yaouba, and Tahir Mahamat, members of the “3R” rebel group. Human Rights Watch has documented the events.  

“The Special Criminal Court’s first trial is a landmark moment for victims in the Central African Republic who have repeatedly called for justice for heinous crimes committed during successive conflicts in the country,” said Esti Tambay, senior International Justice counsel at Human Rights Watch. “This novel court – which combines international and domestic experience to hold those responsible for grave crimes to account – could be an important justice model for other countries to consider.” 

The SCC became operational in 2018 to help limit widespread impunity for serious crimes in the Central African Republic. The court is staffed by both international and national judges and prosecutors, and benefits from international assistance. It has the authority to try grave crimes committed during the country’s armed conflicts since 2003.  

The SCC is conducting investigations in tandem with the ICC, the global permanent court of last resort, which currently has four suspects in custody regarding charges of crimes committed in the Central African Republic. The ICC can play an important role in pursuing cases involving more senior leadership, while the SCC seeks to conduct trials in a wider set of cases in the country’s capital, Bangui. 

“The courts should be strategic in their coordination to maximize their combined efforts at securing justice,” Tambay said. “All countries committed to justice have an important role to play in supporting these courts with much-needed funding and to carry out arrests.” 

Drug use severity in adolescence affects substance use disorder risk in adulthood

People who reported multiple symptoms consistent with severe substance use disorder at age 18 exhibited two or more of these symptoms in adulthood, according to a new analysis of a nationwide survey in the United States.

These individuals were also more likely, as adults, to use and misuse prescription medications, as well as self-treat with opioids, sedatives, or tranquillizers. Published today in JAMA Network Open, the study is funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

While use of alcohol, cannabis, or other drugs is common among adolescents, previous studies have suggested that most teens reduce or cease drug use as they enter adulthood. However, this study indicates that adolescents with multiple symptoms of substance use disorder – indicating higher severity – do not transition out of symptomatic substance use. 

“Screening adolescents for drug use is extremely important for early intervention and prevention of the development of substance use disorder,” said Nora Volkow, M.D., director of NIDA. “This is critical especially as the transition from adolescence to adulthood, when brain development is still in progress, appears to be a period of high risk for drug use initiation.” Dr. Volkow further discusses the findings and implications of this study in a related commentary(link is external).

Researchers in this study argue that key knowledge gaps currently hinder the initiation of screening, diagnosis, prevention, and treatment efforts for teens with substance use disorders. For example, previous methods evaluating persistence of substance use disorder tended to treat substance use disorder as one broad category, without looking at severity. They also failed to account for the possibility of polysubstance use, whereby individuals may use multiple drugs or switch the types of drugs they use as they grow older.

The NIDA-funded Monitoring the Future Panel study at the University of Michigan-Ann Arbor helped close this research gap by examining substance use behaviors and related attitudes among 12th graders through their adulthood in the United States. Since 1976, the study has surveyed panels of students for their drug use behaviors across three time periods: lifetime, past year, and past month. In this study, researchers looked primarily at a subgroup of 5,317 12th graders first evaluated between 1976 and 1986, who were followed with additional surveys at two-year, then five-year intervals for up to 32 years, until they reached age 50. Among the respondents, 51% were female and 78% were white.

The research team examined the relationship between substance use disorder symptom severity at age 18 and prescription drug use, prescription drug misuse, and substance use disorder symptoms up to age 50 in these individuals.

To measure severity of substance use disorder symptoms in adolescence, researchers recorded the number of substance use disorder symptoms that participants reported in response to initial survey questions. These questions were based on criteria for alcohol, cannabis, and “other drug” use disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The researchers categorized substance use disorder symptoms into five levels of severity: exhibiting no symptoms, one symptom, two to three symptoms, four to five symptoms, and six or more symptoms. Symptoms included, but were not limited to, substance use resulting in a failure to fulfill major role obligations and repeating substance use even when dangerous to health.

Approximately 12% of surveyed teens indicated “severe” substance use disorder, defined by this study as reporting six or more symptoms. Among this group, more than 60% exhibited at least two symptoms of substance use disorder in adulthood – an association found across alcohol, cannabis, and other drug use disorders. By comparison, roughly 54% of teens reporting two to three symptoms – indicative of “mild” substance use disorder – had two or more substance use disorder symptoms in adulthood.  Higher severity of substance use disorder symptoms at age 18 also predicted higher rates of prescription drug misuse in adulthood.  

Overall, more than 40% of surveyed 18-year-old individuals reported at least two substance use disorder symptoms (across all substances). More than half of the individuals who were prescribed and used opioids, sedatives, or tranquilizers as adults also reported two or more symptoms at age 18. This finding underlines the importance of strategies to increase safety and properly assess a potential history of substance use disorder symptoms when prescribing controlled medications to adults.

“Teens with substance use disorder will not necessarily mature out of their disorders, and it may be harmful to tell those with severe symptoms that they will,” said Dr. Sean Esteban McCabe, senior author of this study and director of the Center for the Study of Drugs, Alcohol, Smoking and Health at University of Michigan. “Our study shows us that severity matters when it comes to predicting risk decades later, and it’s crucial to educate and ensure that our messaging to teens with the most severe forms of substance use disorder is one that’s realistic. We want to minimize shame and sense of failure for these individuals.”

The authors note that more research is needed to uncover potential neurological mechanisms and other factors behind why adolescents with severe substance use disorder symptoms are at increased risk of drug addiction and misuse in adulthood. Characterizing possible causes of more severe substance use disorder could help improve understanding of vulnerability to chronic substance use and help make prevention and treatment strategies more effective.

NIH begins clinical trial evaluating second COVID-19 booster shots in adults

A Phase 2 clinical trial evaluating various additional COVID-19 booster shots has begun enrolling adult participants in the United States. The trial aims to understand if different vaccine regimens—prototype and variant vaccines alone and in combinations—can broaden immune responses in adults who already have received a primary vaccination series and a first booster shot. The study, known as the COVID-19 Variant Immunologic Landscape (COVAIL) trial, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Colorized scanning electron micrograph of a cell (purple) infected with a variant strain of SARS-CoV-2 virus particles (pink), isolated from a patient sample. NIAID

“We are looking beyond the Omicron variant to determine the best strategy to protect against future variants,” said NIAID Director Anthony S. Fauci, M.D. “This trial will help us understand if we can use prototype and variant vaccines alone or together to shift immune responses to cover existing and emerging COVID-19 variants.”

Despite waning protection against infection and mild illness during the Omicron wave, COVID-19 vaccines available in the United States so far have maintained durable protection against severe COVID-19. However, NIAID is preparing for the possibility of future variants evading protection against currently available COVID-19 vaccines.

COVID-19 vaccine manufacturers can adjust prototype vaccines to target specific variants, a process similar to how manufacturers update seasonal influenza vaccines every year to target circulating strains. However, predicting if, when and where new COVID-19 variants will emerge and how they will affect the population, remains challenging. Studies(link is external) indicate that Omicron has a combination of mutations that make it substantially different from prior SARS-CoV-2 variants. Should a new variant emerge that more closely resembles ancestral SARS-CoV-2 or, for example, the Delta variant, an Omicron-specific vaccine may not offer substantial protection. An individual’s response to booster shots may also be impacted by their history of prior infection and vaccination, or both, and what type of COVID-19 vaccines they received.

Vaccine manufacturers have previously studied some variant vaccine candidates and are currently conducting clinical trials of Omicron-specific vaccines. The COVAIL trial will gather data on the immune responses induced by prototype vaccines and variant vaccine candidates—including bivalent vaccines, which target two SARS-CoV-2 variants—to inform booster shot recommendations.

The first stage of this trial is being conducted in collaboration with Moderna, Inc., based in Cambridge, Massachusetts, and Moderna is manufacturing the study vaccines that will be administered. The trial will be adapted to enroll more participants to evaluate additional vaccine platforms and variant vaccines from other manufacturers as needed to further inform public health decisions. Participants will be monitored for symptoms and adverse events following vaccination and will be asked to return to the clinic during set times over the course of 12-14 months to provide blood samples. Investigators will evaluate the samples in the laboratory to measure and characterize immune responses to SARS-CoV-2 strains. Investigators aim to have initial findings available by August 2022.

Nadine Rouphael, M.D., director of the Hope Clinic at the Emory Vaccine Center in Atlanta, and Angela Branche, M.D., associate professor of medicine at the University of Rochester Medical Center in New York, are leading the trial. Site investigators at 24 clinics are enrolling 600 participants 18 years and older who already have received a primary COVID-19 vaccination series and booster shot. Participants are randomly assigned to one of six vaccine regimens:

Sudan: ICC Holds First Darfur Trial

 The International Criminal Court’s trial of Ali Kosheib, or Kushayb, will open on April 5, 2022, and offers the first opportunity to see a leader face prosecution for massive crimes committed in Darfur nearly 20 years ago, Human Rights Watch said.

Kosheib’s trial is a long-awaited chance for victims and communities terrorized by the notorious Janjaweed militia and government forces in Darfur to see a leader held to account

Human Rights Watch issued a question-and-answer document and a video ahead of the trial.  

“Kosheib’s trial is a long-awaited chance for victims and communities terrorized by the notorious Janjaweed militia and government forces in Darfur to see a leader held to account,” said Elise Keppler, associate international justice director at Human Rights Watch. “In the face of steep odds and no other credible options, the ICC is serving as the crucial court of last resort for Darfuris.”

The video focuses on the significance of the trial and on what else is needed by the Sudanese authorities to advance justice for atrocities committed in Darfur. The question-and-answer document covers:  

“For all these years, those implicated in serious crimes and other abuses in Darfur have largely suffered no consequences, and in some instances, have even been rewarded,” Keppler said. “Would-be abusers should take note that they can end up in court even if it is slow going. Now, Sudanese authorities should surrender the remaining fugitives, including former president Omar al-Bashir, so victims have the opportunity to also see them held to account.”

Ali Kosheib, or Kushayb, is the nom de guerre of Ali Mohammed Ali, identified by the International Criminal Court (ICC) as Ali Mohammed Ali Abd–Al-Rahman. Kosheib is believed to have been the principal leader of the Janjaweed militias in the Wadi Saleh area of West Darfur. He also held commanding positions in Sudanese government auxiliary forces, the Popular Defense Forces and Central Reserve Police.

In early 2003, the Janjaweed worked alongside the Sudanese government forces during its armed conflict with rebel groups to carry out a systematic campaign of “ethnic cleansing.” The campaign targeted civilians from African Fur, Masalit, and Zaghawa ethnic groups, from which the members of the rebel groups were drawn. Attacking from the air and land, Sudanese government forces and allied militias killed, raped, and forcibly displaced more than 2 million people from their homes and land. The Sudanese government recruited, armed, and trained the Janjaweed forces.

NIH launches program to offer molecular characterization of childhood cancers

In support of President Biden’s Cancer Moonshot℠ goal of fostering data sharing in cancer research, the National Cancer Institute, part of the National Institutes of Health, has launched the Molecular Characterization Initiative for pediatric tumors.

The program offers tumor molecular characterization, also called biomarker testing, to children, adolescents, and young adults with newly diagnosed central nervous system tumors who are being treated at hospitals that are affiliated with the Children’s Oncology Group (COG)(link is external), an NCI-supported clinical trials group that includes more than 200 hospitals and institutions that treat most children diagnosed with cancer in the United States.

The Molecular Characterization Initiative is offered through NCI’s Childhood Cancer Data Initiative, which was launched in 2019 to promote data sharing and collection of new data among researchers who study childhood cancers.

Children, adolescents, and young adults diagnosed with a central nervous system cancer across the United States will be eligible to receive molecular characterization of their tumors free of charge through this voluntary program. DNA and RNA from tumor and blood samples will be analyzed to help make an accurate diagnosis and to understand what is causing or driving the cancer. The Molecular Characterization Initiative will expand later in 2022 to include soft tissue sarcomas and other rare tumors.

“The ultimate dream has really been for every child with cancer to have a state-of-the-art diagnosis and the safest and most effective therapy,” said Brigitte C. Widemann, M.D., special advisor to the NCI director for childhood cancer. “The Molecular Characterization Initiative is a transformative collaboration that will entail participation of the entire community.”

Having a precise diagnosis based on the molecular characteristics of a patient’s tumor can help doctors choose the most effective and potentially least toxic treatment for each child. Data on the molecular changes seen across childhood cancers can also help researchers better understand the molecular causes of childhood cancers and accelerate the development of new, more effective, and potentially less toxic treatments, especially for rare childhood cancers for which treatment options are limited. 

“The game changer for patients is that we’re going to understand the patient’s disease precisely and comprehensively in a way that we’ve done piecemeal so far,” said Douglas S. Hawkins, M.D., group chair of COG.

Previously, comprehensive tumor molecular characterization was available to children enrolling in some clinical trials or to those being treated at larger institutions with internal resources to offer such state-of-the-art diagnostics. Data on tumor biomarkers were stored exclusively at the hospital or institution where a child was treated, with limited sharing of data among institutions. The new program will make tumor molecular characterization broadly available for children throughout the country. Moreover, the data collected will be available in a central location so that childhood cancer researchers can learn from the data and use it to inform future studies.

“We can help make molecular characterization available throughout the country so that it will be a standard of care that every child can get,” said Maryam Fouladi, M.D., COG’s central nervous system tumor disease committee leader. “An accurate molecular diagnosis can inform optimal treatment for every child.”

For example, Dr. Fouladi explained, some childhood cancers, such as gliomas, can be misdiagnosed. “We can apply molecular diagnostics to a child diagnosed with a high-grade glioma and find out that it is actually a low-grade glioma or an entirely different tumor, which may need very different treatments and have a very different outcome,” she said. “Molecular diagnostics can really contribute to getting the correct diagnosis, offering the optimal treatment and, ultimately, improving the patient’s outcome.”

In addition to providing detailed information about a cancer to use in making an accurate diagnosis, the data can also be used to determine whether a child is eligible for a clinical trial. Molecular characterization can reveal, for example, whether a child has a specific cancer subtype that is eligible for a clinical trial evaluating a new treatment explicitly designed for that subtype.

Enrollment in the Molecular Characterization Initiative is initially offered through participation in Project:EveryChild(link is external), a childhood cancer registry maintained by COG (APEC14B1). Initial participants will include newly diagnosed children, adolescents, and young adults ages 25 years and younger at the time of diagnosis. Young adults over the age of 25 who are being screened for eligibility into a COG clinical trial may also be included.

Tumor and blood samples from participants will be sent to an accredited lab for analysis, and the results will be available to patients and their families within 21 days. The molecular data will also be aggregated into a database available to researchers for future studies, such as those exploring why some tumors become resistant to therapies they initially responded to or what factors increase the risk of treatment-related side effects. Personal information that could be used to identify a participant will be removed before data are put into the database.

Dr. Widemann said the Molecular Characterization Initiative is a program the childhood cancer community can easily get behind. “To be able to apply the best tools to make the most accurate diagnosis so that the most effective treatment can be prescribed, that’s a goal that I think physicians and families can all align around,” she said.

Hydrocortisone does not prevent lung complications in extremely preterm infants

Hydrocortisone is no more effective than a placebo at preventing damage that can result from oxygen and ventilator therapy necessary to keep preterm infants alive, according to research funded by the National Institutes of Health.

The study of a potential treatment for the condition, known as bronchopulmonary dysplasia, appears in the New England Journal of Medicine.

In recent years, hydrocortisone was considered as a replacement for the widely used drug dexamethasone in the prevention of bronchopulmonary dysplasia. Both drugs inhibit the inflammation thought to contribute to BPD, but animal studies suggested that hydrocortisone would have fewer effects on the developing brain. Infants born preterm have higher rates of death and disability(link is external).

The study enrolled 800 infants born before the 30th week of pregnancy who had been on a ventilator for at least seven days. From 14 days to 28 days, in addition to receiving standard care and ventilator therapy, infants were randomly assigned to receive either hydrocortisone or a placebo.

Of the hydrocortisone-treated infants, 16.6% survived to 36 weeks without moderate or severe bronchopulmonary dysplasia, which did not differ significantly from 13.2% in the placebo group. The rate of neurodevelopmental impairment did not differ significantly between the groups (36.9% vs. 37.3%). The hydrocortisone group was more likely to need drug treatment for hypertension than the placebo group (4.3% vs. 1.0%).