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More than 1.2 million adolescents die every year, nearly all preventable

WHO and partners recommend actions to improve adolescent health.
More than 3000 adolescents die every day, totalling 1.2 million deaths a year, from largely preventable causes, according to a new report from WHO and partners. In 2015, more than two-thirds of these deaths occurred in low- and middle-income countries in Africa and South-East Asia. Road traffic injuries, lower respiratory infections, and suicide are the biggest causes of death among adolescents.

Most of these deaths can be prevented with good health services, education and social support. But in many cases, adolescents who suffer from mental health disorders, substance use, or poor nutrition cannot obtain critical prevention and care services – either because the services do not exist, or because they do not know about them.

In addition, many behaviours that impact health later in life, such as physical inactivity, poor diet, and risky sexual health behaviours, begin in adolescence.

“Adolescents have been entirely absent from national health plans for decades,” says Dr Flavia Bustreo, Assistant Director-General, WHO. “Relatively small investments focused on adolescents now will not only result in healthy and empowered adults who thrive and contribute positively to their communities, but it will also result in healthier future generations, yielding enourmous returns.”

Data in the report, Global accelerated action for the health of adolescents (AA-HA!): Guidance to support country implementation, reveal stark differences in causes of death when separating the adolescent group by age (younger adolescents aged 10–14 years and older ones aged 15–19 years) and by sex. The report also includes the range of interventions – from seat-belt laws to comprehensive sexuality education – that countries can take to improve their health and well-being and dramatically cut unnecessary deaths.

Road injuries top cause of death of adolescents, disproportionately affecting boys

In 2015, road injuries were the leading cause of adolescent death among 10–19-year-olds, resulting in approximately 115 000 adolescent deaths. Older adolescent boys aged 15–19 years experienced the greatest burden. Most young people killed in road crashes are vulnerable road users such as pedestrians, cyclists and motorcyclists.

However, differences between regions are stark. Looking only at low- and middle-income countries in Africa, communicable diseases such as HIV/AIDS, lower respiratory infections, meningitis, and diarrhoeal diseases are bigger causes of death among adolescents than road injuries.

Lower respiratory infections and pregnancy complications take toll on girls’ health

The picture for girls differs greatly. The leading cause of death for younger adolescent girls aged 10–14 years are lower respiratory infections, such as pneumonia – often a result of indoor air pollution from cooking with dirty fuels. Pregnancy complications, such as haemorrhage, sepsis, obstructed labour, and complications from unsafe abortions, are the top cause of death among 15–19-year-old girls.

Adolescents are at very high risk of self-harm and suicide

Suicide and accidental death from self-harm were the third cause of adolescent mortality in 2015, resulting in an estimated 67 000 deaths. Self-harm largely occurs among older adolescents, and globally it is the second leading cause of death for older adolescent girls. It is the leading or second cause of adolescent death in Europe and South-East Asia.

A vulnerable population in humanitarian and fragile settings

Adolescent health needs intensify in humanitarian and fragile settings. Young people often take on adult responsibilities, including caring for siblings or working, and may be compelled to drop out of school, marry early, or engage in transactional sex to meet their basic survival needs. As a result, they suffer malnutrition, unintentional injuries, pregnancies, diarrhoeal diseases, sexual violence, sexually-transmitted diseases, and mental health issues.

Interventions to improve adolescent health

“Improving the way health systems serve adolescents is just one part of improving their health,” says Dr Anthony Costello, Director, Maternal, Newborn, Child and Adolescent Health, WHO. “Parents, families, and communities are extremely important, as they have the greatest potential to positively influence adolescent behaviour and health.”

The AA-HA! Guidance recommends interventions across sectors, including comprehensive sexuality education in schools; higher age limits for alcohol consumption; mandating seat-belts and helmets through laws; reducing access to and misuse of firearms; reducing indoor air pollution through cleaner cooking fuels; and increasing access to safe water, sanitation, and hygiene. It also provides detailed explanations of how countries can deliver these interventions with adolescent health programmes.

Top 5 causes of death for all adolescents aged 10–19 years in 2015
Cause of death Number of deaths
1. Road traffic injury 115 302
2. Lower respiratory infections 72 655
3. Self-harm 67 149
4. Diarrhoeal diseases 63 575
5. Drowning 57 125


Top 5 causes of death for males aged 10–19 years in 2015
Cause of death Number of deaths
1. Road traffic injury 88 590
2. Interpersonal violence 42 277
3. Drowning 40 847
4. Lower respiratory infections 36 018
5. Self-harm 34 650


Top 5 causes of death for females aged 10–19 years in 2015
Cause of death Number of deaths
1. Lower respiratory infections 36 637
2. Self-harm 32 499
3. Diarrhoeal diseases 32 194
4. Maternal conditions 28 886
5. Road traffic injury 26 712


Psoriasis Response Falls as Comorbidities Rise

Two-thirds of patients with moderate or severe plaque psoriasis had comorbid conditions at baseline, which appeared to blunt the effect of treatment, according to a study reported here.

Overall, 64% of patients had one or more comorbid conditions at the start of treatment, and some of the patients had new comorbid diagnoses during follow-up. The proportion of patients who achieved disease clearance decreased as the number of comorbidities increased, as reported at the European Academy of Dermatology and Venereology congress.

“Patients with no comorbidities at baseline reported almost double the clearance rate of those patients with three or more comorbidities at baseline,” said Finn Ziegler, of LEO Pharma in Ballerup, Denmark. “More insights are needed on how different treatments can influence skin clearance in patients with comorbidities.”

Numerous studies have documented a high prevalence of comorbid conditions in patients with plaque psoriasis. However, the impact of comorbidities on treatment-induced disease clearance remained unclear, said Ziegler.

In an effort to clarify the relationship between comorbidities and clearance, an international team of investigators performed a 12-month observational study involving 846 patients with newly diagnosed moderate or severe psoriasis in the United States and Europe. All the patients were either initiating treatment with a biologic agent or switching from one biologic to another at the time of enrollment.

Patients self-reported baseline comorbidities by means of a questionnaire. Investigators also reported patients’ comorbidities at baseline and during the follow-up period by means of a separate questionnaire. The physician questionnaire had a checklist of selected conditions identified prior to the start of patient enrollment.

The study population had a mean age of 47.4, and men accounted for about two thirds of the population. The patients had a median psoriasis duration of 18.4 years, mean Psoriasis Area and Severity Index (PASI) score of 14.3, and 40% had prior exposure to a biologic agent. The mean body mass index for the study population was 29.4.

Ziegler said 541 patients had one or more comorbidities prior to starting or switching biologic treatment, including 60% of patients enrolled in Europe and 72.4% of patients from the U.S. The most commonly reported comorbid conditions were hypertension (33.5%), psoriatic arthritis (28.1%), hyperlipidemia (20.9%), diabetes (13.9%), and depression (13.7%). During follow-up, 31 patients developed new comorbid conditions, consisting of anxiety in five patients; hypertension in five; psoriatic arthritis in four; and depression, hyperlipidemia, and other rheumatologic conditions in three patients each.

The subgroup of patients with concomitant psoriatic arthritis consisted of 23.4% of patients with no prior biologic therapy and 35.3% of those previously treated with biologic therapy.

Comparison comorbidity burden and response to treatment, investigators found that 31% of patients with no comorbid conditions at baseline had disease clearance (PASI 100) at 6 months, as compared with 16.5% of patients who had three or more comorbid conditions at enrollment. A similar disparity was observed after 12 months of treatment.

Ziegler acknowledged several limitations of the study. The descriptive design precluded the possibility of assessing causality. Various confounding factors could have affected the results. Rates of psoriatic arthritis differed between the patient and investigator questionnaires, suggesting potential underreporting of that condition and the other comorbidities.

Stem Cells From Baby Teeth Could Be Used to Bring Back a Dead Tooth

Don’t throw out those baby teeth, they have incredible potential.

main article image

Stem cells taken from baby teeth could be used to repair dental injuries and fix dead teeth in the future, according to new research.

Scientists have announced they’ve been able to use the cells to patch up permanent teeth in children that have not yet fully grown.

The regenerative nature of stem cells – those powerful cells that can morph and divide to repair almost any part of the body – enabled researchers to successfully replenish the soft inner tissue (or dental pulp) in the teeth of 30 patients in a clinical trial in China.

Further down the line the same technique could be used to repair adult teeth as well, replacing the blood vessels and nerve connections that are often gone forever when a tooth take a serious knock.

baby teeth stem 2Regenerated dental pulp. (University of Pennsylvania)

“This treatment gives patients sensation back in their teeth,” says one of the team, Songtao Shi from the University of Pennsylvania. “If you give them a warm or cold stimulation, they can feel it; they have living teeth again.”

“So far we have follow-up data for two, two and a half, even three years, and have shown it’s a safe and effective therapy.”

As the researchers point out, nearly half of all kids suffer some kind of injury to a tooth during childhood, and if that happens while their permanent teeth are still growing, blood supply and root development can be affected, sometimes leaving a “dead” tooth.

Dentists already use a treatment called apexification to try and encourage root development, but it’s not an ideal solution, and doesn’t do anything to replace lost tissue – that dental pulp inside our teeth.

Shi and his team have been working for a decade with dental stem cells taken from baby teeth, technically known as human deciduous pulp stem cells (hDPSC).

The clinical trial most recently carried out involved 30 kids treated with the new method and 10 kids treated using apexification.

For those undergoing the new treatment, stem cells were cultured in a lab and them implanted back into the injured tooth.

The results showed that the injured teeth of the children who had been given hDPSCs had increased blood flow and thicker dentin, as well as more signs of healthy root development. A year afterwards, only those on the new treatment had regained some sensation in their damaged teeth.

One of the kids unfortunately re-injured the same tooth and had to have it extracted – but that did give researchers chance to examine it again. They found the stem cells had regenerated dentin-producing cells, connective tissue and blood vessels, which all help to make up dental pulp.

This is all very encouraging but there’s still plenty of work to do.

Broader tests need to be carried out to make sure the procedure works, and the team also wants to explore how stem cells not taken from patients’ own baby teeth might react inside the body – when it comes to adult dental injuries of course, the baby teeth will be long gone.

For now mark this down as another encouraging step forward in the field of dental repair.

Last year researchers identified a drug called Tideglusib that can activate stem cells inside the tooth’s pulpy centre and potential regrow some of the tissue inside. No human trials have been carried out as yet, but work is ongoing.

If treatments like these can eventually be made reliable and safe enough, we should see more children and adults with a healthier set of teeth.

“For me, the results are very exciting,” says Shi. “To see something we discovered take a step forward to potentially become a routine therapy in the clinic is gratifying.”

Serious Infection Risk with Biologics for Atopic Dermatitis

Off-label use of biologic agents to treat refractory atopic dermatitis posed a significant risk of serious infection as compared with systemic nonbiologic agents, data on almost 400,000 patients showed.

A propensity-matched analysis showed that treatment with a biologic agent doubled the risk of hospitalization for a serious bacterial or opportunistic infection as compared with high-potency topical steroids or nonbiologic systemic therapy. Infection risk also varied substantially among nonbiologic systemic agents, with cyclosporine posing the lowest risk and azathioprine and mycophenolate the greatest risk, as reported here at the European Academy of Dermatology and Venereology congress.

“This is the largest comparative safety evaluation of its kind to date in adult patients with atopic dermatitis,” said Mia Schneeweiss, a student at Harvard Medical School and Brigham and Women’s Hospital in Boston. “Biologics were associated with a greater risk of serious infection requiring hospitalization than either nonbiologic systemics or topical steroids.”

The analysis did not include patients treated with newer biologic agents specifically approved for atopic dermatitis, such as dupilumab (Dupixent). Investigators intend to update the analysis with data on outcomes with the newer agents, as well as long-term outcomes with all the treatments, she added.

The study had its genesis in the increasing use of systemic nonbiologic immunomodulatory drugs and systemic biologic agents to treat atopic dermatitis that is inadequately controlled by topical steroids. Mixed results have emerged from studies use of biologic agents to treatment recalcitrant atopy; however, experience with systemic biologic and nonbiologic agents in other conditions (such as psoriasis and rheumatoid arthritis) has shown an increased risk of bacterial infections, Schneeweiss noted.

“Few population-based studies have evaluated the safety of off-label use of these systemic agents for treating severe atopic dermatitis,” she said. “Additionally, comparative safety data among nonbiologic and biologic immunomodulatory agents in the treatment of atopic dermatitis is limited.”

In an effort increase the evidence base, investigators undertook an analysis of a commercial insurance claims database encompassing 2003-2016 and 180 million lives. They used diagnostic codes to identify all adults with a diagnosis of atopic dermatitis and initiating treatment. Patients with other indications for any of the medications of interest (psoriasis, arthritis, organ transplantation, etc.) were excluded.

The primary outcome was first occurrence of hospitalization for a serious bacterial or opportunistic infection. Patient characteristics were assessed 6 months before the study and followed for an additional 6 months.

The study consisted of two cohort analyses. The first involved patients who initiated treatment with a low-potency topical corticosteroid and subsequently had treatment escalation to one of three therapeutic categories: high-potency topical corticosteroids, biologics and disease-modifying drugs (including anti-TNF agents, rituximab [Rituxan], and tofacitinib [Xeljanz], and nonbiologic systemic therapy (methotrexate, cyclosporine, azathioprine, prednisone, and mycophenolate).

The second cohort comprised patients who started treatment with any type of topical corticosteroid and subsequently had treatment escalation to a biologic or systemic nonbiologic agent.

The first cohort included 396,734 patients who initiated treatment with a high-potency topical corticosteroid and 403 patients who started treatment with a biologic agent. The second cohort included 153,890 patients who initiated treatment with a systemic nonbiologic agent and 2,116 who who started a biologic drug.

In the first cohort, patients who escalated to a high-potency topical steroid had a total of 1,039 qualifying hospitalizations for serious infection, resulting in a rate of 2.62 per 1,000. That compared with 16 events in the 403 patients who initiated treatment with a biologic agent, resulting in a rate of 39.70 per 1,000. An unadjusted analysis produced a relative risk of 15.16 for patients treated with biologics.

The second cohort analysis showed 1,239 hospitalizations for infection in the patients who were new users of systemic nonbiologic agents (8.05/1,000) versus 47 hospitalizations among new users of biologic therapies (22.21/1,000). Comparison of the two groups yielded a relative risk of 2.76 for the patients who received biologic therapy.

A multivariate analysis with propensity matching yielded similar relative risks for the two cohorts: 2.74 for the comparison of biologics versus high-potency topical corticosteroids and 2.16 for the comparison of biologics versus systemic nonbiologic agents.

Investigators also compared the relative risk of infection-related hospitalization for the five systemic nonbiologic agents. Cyclosporine emerged with the lowest overall relative risk, ranging from 0.17 to 0.55 in comparisons with other four systemic nonbiologic, followed by prednisone and methotrexate. Mycophenolate was associated with the highest relative risk (1.64 to 5.88), and azathioprine had a two- to fourfold higher risk versus all other agents except mycophenolate