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Monthly Archives: February 2017

Chemical Found in Blood Holds Clues to Survival

Even within the normal range, higher bilirubin levels appear to be associated with reduced risks of lung cancer, chronic obstructive pulmonary disease (COPD), and death, a longitudinal, prospective analysis of a large database showed.

For every 0.1-mg/dL increase in bilirubin level, the rate of lung cancer dropped by 8 percent in men and 11 percent in women, according to Laura Horsfall, MSc, of University College London, and colleagues.

In addition, the same incremental increase in bilirubin was associated with a 6 percent decline in the rate of COPD and a 3 percent decline in mortality for both sexes, the researchers reported in the Feb. 16 issue of the Journal of the American Medical Association.

“Based on our findings, bilirubin levels within the normal range appear to capture information about patients that may reflect a combination of environmental and genetically determined susceptibility to respiratory diseases,” they wrote.

Most people are familiar with bilirubin because of its role in jaundice — the yellowing of the skin that is sometimes seen in newborns but is also associated with liver disease.

Bilirubin is actually a byproduct of the turn over of red blood cells — the cells that carry oxygen throughout the body. Healthy individuals constantly replace old red blood cells with new ones. As the old cells are broken down they produce bilirubin, a chemical characterized by a distinctive yellow color.

The spleen and the liver taking in bilirubin and use it to break down or metabolize other substances into bile, which is used to aid digestion.

Although the study cannot establish causality for any of the relationships, there is some experimental evidence that bilirubin has benefits for respiratory health because of its cytoprotective properties, including antioxidant, anti-inflammatory, and antiproliferative effects, according to the researchers.

They noted that a better understanding of the possible mechanisms linking bilirubin levels to lung cancer, COPD, and death may lead to potential therapies that target the activity of UGT1A1, a liver enzyme responsible for converting insoluble bilirubin to an excretable form.

Horsfall and her colleagues examined data from the Health Improvement Network, a U.K. primary care research database.

Their analysis included 504,206 patients ages 20 and older from 371 practices. All of the patients had recorded serum bilirubin levels but no evidence of hepatobiliary or hemolytic disease.

Median bilirubin levels were 0.64 mg/dL in men and 0.53 mg/dL in women.

Through a median follow-up of eight years, there were 1,341 incident cases of lung cancer, 5,863 incident cases of COPD, and 23,103 all-cause deaths. The corresponding rates per 10,000 person-years were 2.5, 11.9, and 42.5.

For men, the rate of lung cancer per 10,000 person-years dropped from 5.0 in the lowest decile of bilirubin levels to 3.0 in the fifth decile. Similar declines were seen for COPD (19.5 to 14.4) and death (51.3 to 38.1).

The findings were similar for all outcomes in women, and the declines in both sexes remained significant after adjustment for age, body mass index, systolic blood pressure, smoking, alcohol intake, and a measure of social deprivation.

The authors acknowledged some limitations of the study, including possible residual confounding by unmeasured environmental exposures or race/ethnicity and the inability to establish causality for the observed relationships.

Marijuana Users at Risk for Early Psychosis

Data on more than 22,000 patients with psychosis showed an onset of symptoms almost three years earlier among users of cannabis compared with patients who had no history of substance use.

The age of onset also was earlier in cannabis users compared with patients in the more broadly characterized category of substance use, investigators reported online in Archives of General Psychiatry.

“The results of this study provide strong evidence that reducing cannabis use could delay or even prevent some cases of psychosis,” Dr. Matthew Large, of the University of New South Wales in Sydney, Australia, and co-authors wrote in conclusion.

“Reducing the use of cannabis could be one of the few ways of altering the outcome of the illness because earlier onset of schizophrenia is associated with a worse prognosis and because other factors associated with age at onset, such as family history and sex, cannot be changed.”

Psychosis has a strong association with substance use. Patients of mental health facilities have a high prevalence of substance use, which also is more common in patients with schizophrenia compared with the general population, the authors wrote.

Several birth cohort and population studies have suggested a potentially causal association between cannabis use and psychosis, and cannabis use has been linked to earlier onset of schizophrenia. However, researchers in the field remain divided over the issue of a causal association, the authors continued.

Attempts to confirm an earlier onset of psychosis among cannabis users have been complicated by individual studies’ variation in methods used to examine the association. The authors sought to resolve some of the uncertainty by means of meta-analysis.

A systematic search of multiple electronic databases yielded 443 potentially relevant publications. The authors whittled the list down to 83 that met their inclusion criteria: All the studies reported age at onset of psychosis among substance users and nonusers.

The studies comprised 8,167 substance-using patients and 14,352 patients who had no history of substance use. Although the studies had a wide range of definitions of substance use, the use was considered “clinically significant” in all 83 studies. None of the studies included tobacco in the definition of substance use.

The studies included a total of 131 patient samples.

Substance use included alcohol in 22 samples, cannabis in 41, and was simply defined as “substance use” in 68 samples.

Alcohol use was not significantly associated with earlier age at onset of psychosis.

On average, substance users were about 2 years younger than nonusers were. The effect of substance use on age at onset was greater in women than in men, but not significantly so. Heavy use was associated with earlier age at onset compared with light use and former use, but also not significantly different, the authors reported.

Substance users were two years younger at the onset of psychosis compared with nonusers. Age at onset was 2.7 years earlier among cannabis users compared with nonusers.

Acknowledging limitations of the study, the authors cited the lack of information on tobacco use and its association with earlier age at onset of psychosis, and the lack of data on individual patients inherent in all meta-analyses.

Despite the limitations, the authors said the findings have potentially major clinical and policy implications.

“This finding is an important breakthrough in our understanding of the relationship between cannabis use and psychosis,” they wrote in conclusion. “It raises the question of whether those substance users would still have gone on to develop psychosis a few years later.”

“The results of this study confirm the need for a renewed public health warning about the potential for cannabis use to bring on psychotic illness,” they added.

Painkiller Use Common Among NFL Players

Retired National Football League players who abused opioid painkillers while active were most likely to use and abuse the same drugs after leaving the sport, the results of a telephone survey and analysis found.

The survey found more than half of the retired NFL players interviewed used opioidpainkillers during their career. Of those, 71 percent reported misusing the drugs while playing, and 15 percent said they still abuse the prescription medication, Dr. Linda B. Cottler, of Washington University School of Medicine, and colleagues reported online in Drug and Alcohol Dependence.

The former broadcaster and NY Giants great, Frank Gifford, said, “pro football is like nuclear warfare. There are no winners, only survivors.”

The findings from Cottler’s survey support Gifford’s assessment.

An analysis of survey data showed the rate of opioid misuse while the retired players were active in the NFL was roughly three times greater than the lifetime rate of nonmedical use of opioids in the general population of approximately the same age.

Misuse in the past 30 days in retired players was seven percent, versus less than two percent in adults 26 and older in the general population. Looking only at men in the general population, the abuse rate is about two and half percent.

The final sample included 644 former players listed in the 2009 Retired NFL Football Players Association Directory who had retired from 1979 to 2006 and had at least one phone number listed.

They completed a phone interview that discussed general demographic data, health status, pain, impairment, alcohol use, prescription opioid use, and illicit drug use. Prescription opioid use was measured for while a player was active as well as over the past 30 days. Participants were categorized into users and nonusers. Users were subcategorized as having used the drugs as prescribed, or having misused them.

Misuse was defined as taking more of the drug than prescribed, using it in a way other than prescribed, using it after a prescription ended, using it for a different reason, or using it without a prescription.

When compared against players prescribed opioids while in the NFL and with those who were non-users during their NFL careers, 17 percent of those who misused while playing used as prescribed in the past 30 days, 15 percent misused in the past 30 days, and 68 percent reported no use.

In a multivariate analysis, moderate to severe pain, undiagnosed concussions, and drinking 20 or more alcoholic drinks a week were the strongest predictors of misuse. Undiagnosed concussions were reported by 81 percent of misusers.

“This association might have been due to the fact that those who choose not to report concussions are the same players who choose not to reveal their pain to a physician, thus managing their pain on their own,” the researchers wrote. “They may believe that if they report a concussion, they will be pulled from active play.”

The researchers noted the study may have been limited by lack of detailed pain information from while a player was active, a small sample size, a more inclusive definition of misuse that included abuse of opioids a player was prescribed, and a sample that included potentially more-healthy-than-average retired footballers — the researchers noted interviews with former players not in the Retired Players Association uncovered “multiple examples of serious and heavy opioid abuse.”

They added that future research could measure number of alcoholic drinks and level of pain while active in the NFL against opioid use and abuse.

Head Injuries Carry Long Term Death Risk

The risk of death after head injury remained significantly increased for as long as 13 years, irrespective of the severity of the injury, results of a case-control study showed.

Overall, patients with a history of head injury had more than a twofold greater risk of death than did two control groups of individuals without head injury.

Among young adults, the risk disparity ballooned to more than a fivefold difference, Scottish investigators reported online in the Journal of Neurology, Neurosurgery and Psychiatry.

“More than 40% of young people and adults admitted to hospital in Glasgow after a head injury were dead 13 years later,” Dr. Thomas M. McMillan, of the University of Glasgow, and coauthors wrote in the discussion of their findings. “This stark finding is not explained by age, gender, or deprivation characteristics.”

“As might be expected following an injury, the highest rate of death occurred in the first year after head injury,” they continued. “However, risk of death remained high for at least a further 12 years when, for example, death was 2.8 times more likely after head injury than for community controls.”

Previous studies of mortality after head injury have focused primarily on early death, either during hospitalization or in the first year after the injury. Whether the excess mortality risk persists over time has remained unclear, the authors noted.

Few studies have compared mortality after head injury with expected mortality in the community. To provide that missing context, McMillan and coauthors conducted a case-control study involving 757 patients who incurred head injuries of varying severity from February 1995 to February 1996 and were admitted to a Glasgow-area hospital.

For comparison, the investigators assembled two control groups, both matched with the cases for age, sex, and socioeconomic status and one matched for duration of hospitalization after injury not involving the head.

One control group was comprised of persons hospitalized for other injured and other comparison group included healthy non-hospitalized adults.

The cases comprised 602 men and 155 women who had a mean age of 43, and almost 70 percent were in the lowest socioeconomic quintile.

At the end of follow-up, 305 of the head-injured patients had died, compared with 215 of the hospitalized control group, and 135 of healthy, non-hospitalized adults.

Mortality after one year remained significantly higher in the head-injury group—34 percent versus 24 percent among the hospitalized comparison group and 16 percent for the healthy non-hospitalized adults.

Overall, the head-injury group had a death rate of 30.99/1,000/ year versus 13.72/1,000/year in the community controls and 21.85/1,000/year in the hospitalized-other injury control group.

The disparity was greater among younger adults (15 to 54), who had a rate of 17.36/1,000/year versus 2.21/1,000/year in the community controls. Older adults in the head injury group had a death rate of 61.47/1,000/year compared with 39.45/1,000/year in the community controls.

“Demographic factors do not explain the risk of death late after head injury, and there is a need to further consider factors that might lead to health vulnerability after head injury and in this way explain the range of causes of death,” the authors wrote in conclusion. “The elevated risk of mortality after mild head injury and in younger adults makes further study in this area a priority.”