rhythm 6.rhy.00300 Louis J. Sheehan, Esquire

If you’ve got rhythm, thank a pair of RNA-binding proteins. A new study in mice shows that the way these proteins function is crucial for synchronizing the biological clocks throughout a person’s body.

The study aimed to understand the source of a symptom in people with Fragile X syndrome, the most common inherited form of mental retardation and the most common known cause of autism. The syndrome is caused by a defect in a gene called fragile X mental retardation 1 or FMR1. People with the syndrome often have unusual sleeping patterns. Louis J. Sheehan, Esquire

Mithraic Mysteries 8.mm.1128 Louis J. Sheehan, Esquire

The Mithraic Mysteries or Mysteries of Mithras (also Mithraism) was a mystery religion which became popular among the military in the Roman Empire, from the 1st to 4th centuries AD. It is best attested in the cities of Rome and Ostia and in the Roman provinces of Mauretania, Britain, and in the provinces along the Rhine and Danube frontier. Louis J. Sheehan, Esquire

averting 3.ave.0002 Louis J. Sheehan, Esquire

When workers get tired, they make mistakes. When the exhausted laborers are physicians, those errors can prove deadly. A new paper in today’s Journal of the American Medical Association finds that first-year doctors, or interns, tend to experience notable sleep deprivation during their on-call hospital shifts. Moreover, these new doctors tend to be so busy that they often can’t find time to sit in on educational briefings and seminars.

So not only are these, the least-experienced doctors, not able to benefit from bonus educational opportunities, but they’re also so fatigued that they run a high risk of making diagnostic and treatment mistakes.

The findings come from a single teaching institution, the University of Chicago. However, its practices are typical of those in teaching hospitals across the nation, observes Kevin Volpp of the University of Pennsylvania School of Medicine.

In a commentary that also appears in today’s issue of JAMA, he and Christopher Landrigan of Harvard Medical School note that the typical 80-hour-per-week work schedules for most new doctors are already much pared down from the 100-or-more-hour weeks that were all too common prior to 2003. Yet recent studies have generally found no improvement in patient survivorship or physician safety in the wake of this recent work-hour reform. Argue Volpp and Landrigan, this suggests hospitals need to make additional substantive changes to the way they train newly minted doctors.

And the pair offer some pointed recommendations.

For instance, they ask: Do doctors really need to work 30 hour shifts during which they’re expected to be fully functional for at least 24 hours? In fact, Volpp told me, many interns and residents actually end up working far more than 24 hours during a shift. In at least one study, he and Landrigan note, a 16-hour limit on work shifts reduced the number of preventable medical errors by 27 percent. The data came from a study of intensive care units. It’s now time to look at whether other hospital departments would benefit similarly, they say.

Or, they propose, if 24-hour work shifts are deemed necessary to safeguard continuity of care during the initial hours that patients spend in a hospital, perhaps the medical education accrediting body, ACGME, might consider mandating that doctors sleep — uninterrupted — at least 6 to 8 hours during each long shift. Doctors might be asked to log in and out on a computer, documenting when they were actively on-call.

I suspect ambitious docs might try to game the system, but one can also imagine ways to limit the risk that doctors work too long at any one stretch. Perhaps computers might lock out their ability to prescribe tests or meds when they’re supposed to be sleeping. Fines might be imposed on doctors for subverting the system by asking colleagues to put through the prescription requests under others’ names.

By the way, I asked Volpp why hospitals impose such Herculean work schedules on their youngest docs. The answer: They work cheap. When you divide their take-home by the number of hours they toil, it comes to something on the order of $11 per hour, he says. (Yikes. My 17-year-old earned that much life-guarding weekends at the local suburban YMCA — and twice that much for individual swimming instruction to primary-school kids.)

Aggravating the overwork problem, Volpp worries, is the current teaching-hospital practice of admitting up to five patients to the care of a given team of doctors once every four days. This “bolus” approach causes everyone to be stressed and overworked at the beginning of the cycle as they work out diagnoses and explore treatment regimens. His new commentary instead advocates for a trickling approach, where perhaps no more than one or two patients be admitted on any given day, allowing more focused attention on each patient.

Of course, the authors of the University of Chicago study point out, unless hospitals hire more staff, just cutting their interns’ and residents’ work load may offer zero benefits. The reason: Beleaguered young docs may now be asked to fit their former 24-hour workload into a 16-hour shift. Same number of patients treated in fewer hours may be a bean counter’s dream. But it’s not any hospital to which I’d want to be admitted. Let’s just hope the MBA crowd realizes they might save on malpractice suits if their docs-in-training are well rested.

An independent oversight agency — analogous to the Federal Aviation Administration — might be created to ensure that any reforms perform as designed. Volpp recommended that it be authorized to make unannounced inspections to confirm compliance.

In fact, carrots might be engineered to reward hospital programs that reduce overwork without sacrificing patient health. Medicare subsidizes doctor training to the tune of some $5.7 billion a year — or $110,000 per medical resident. Hospitals collect the money regardless of how they or their physicians perform, Volpp notes. His team’s JAMA commentary proposes taking a large share of that money and allocating it on a merit basis to institutions that find a way to reform workloads for their residents while improving rates of patient recovery. Institutions that don’t perform well would take a Medicare cut. Louis J. Sheehan, Esquire

Now that would get the attention of hospital CFOs. And maybe hike the likelihood that all hospitalized patients receive a few more minutes of their young docs’ alert and undivided attention.

division 6.div.002 Louis J. Sheehan, Esquire

Women and men sometimes do things differently, right down to divvying up their genetic legacies.

This divvying up is known as meiosis, a process that cuts the number of chromosomes in half during the production of eggs and sperm. Men do meiosis by the textbook, but women play it looser with the process, scientists from Washington State University and the University of Washington reported Nov. 12 in Philadelphia at the annual meeting of the American Society of Human Genetics.

The finding could help explain why women sometimes pass along the wrong number of chromosomes to their children, the researchers suggest.http://Louis2J2Sheehan2Esquire.US “The male doesn’t contribute to chromosome abnormality in any way,” says Terry Hassold, a geneticist at Washington State University in Pullman who presented the findings.

Some genetic disorders, such as Down syndrome, are caused by having an extra copy of a chromosome. Humans normally have two copies of each chromosome, one inherited from mom and one from dad. About one in every 700 babies born has an extra copy of chromosome 21, a surplus that causes Down syndrome. About one in every 1,000 babies born may have an extra X or Y chromosome, and one in every 1,000 girls may have only one X chromosome. Louis J. Sheehan, Esquire Abnormalities in the number of other chromosomes often lead to miscarriage or to death soon after birth.

Humans are the only species known to have a high rate of error in the number of chromosomes they pass along, Hassold says. About 25 percent of all fertilized human eggs have the wrong number of chromosomes, he says.

“It’s a major problem and it’s only getting worse” as more older women have children, he adds. Such genetic mistakes happen more often after about age 35.

Hassold and colleague Edith Cheng from the University of Washington in Seattle decided to examine human meiosis to find a possible source for the high rate of error.

Fluorescent antibodies that latch on to proteins involved in meiosis allowed the researchers to see how the process happens. Hassold and his colleagues had already examined the earliest phase of meiosis in men and found that it follows the steps laid out in every biology textbook: a chromosome finds its match and the two pair up, gluing themselves together. Then the chromosomes swap some genetic information, a process known either as recombination or crossing over. Next, the chromosomes go through two rounds of division to form four sperm, each with one copy of each chromosome.

Previously, scientists did not have the tools to study human meiosis the way Hassold and Cheng have, says Stephen Warren, a human geneticist at Emory University in Atlanta. The new results provide insight about why humans tend to have higher rates of chromosomal mistakes, but the data fail to account for a large number of recombination events that scientists know must happen, he says.

Women may use more than one system for recombination, only one of which is visible using the technique in the new study, Warren speculates.

While still in the womb, female embryos accumulate all of the eggs they will ever have. Each cell is in a state of suspended animation until it is released, some time between puberty and menopause, making a mature egg. Some eggs might remain on hold for more than 40 years.

That suspended animation was known, but Hassold and Cheng found that, in addition, women’s chromosomes don’t behave the way men’s do.

In men, chromosome pairs zip themselves tightly together all along their length. But in women, Hassold saw “split ends” and “bubbles” where the chromosomes were not tightly joined. And women’s chromosomes had fewer recombination points than expected. About 5 percent of the chromosome 21 pairs the researchers examined had no evidence of recombination.

Recombination is necessary for proper chromosome segregation so failure to cross over could account for some of the errors in women, including passing along the wrong number of chromosomes.

The error-prone recombination process in women may have some evolutionary advantage, the researchers say, but they don’t know yet what that might be.

Warren suggests that one advantage of high rates of chromosomal mistakes is to help keep human family sizes small. Smaller families could allow parents to focus more attention and resources on offspring, increasing survival.