Medical Breakthroughs, Recent. Archives

Adult HPV Vaccine Age, Guidelines

“The HPV vaccine is having a significant effect of decreasing cervical cancer. More recently HPV is associated with oral cancer and anal cancer.

HPV goes through latex And many of other sexually transmitted diseases do not. Many adults don’t know that the “safe sex” procedures they use may not work with HPV.

This recent review of this CDC information says that the vaccine has a low side effect rate in adults. The CDC data is established up to age 26. The CDC cannot recommend the vaccines for older adults. Adults older than 26 years who are sexually active should examine this data and balance that with their HPV risks.

Gardasil 9 has the broadest range of efficacy. The Prevents infection by 9 different types of HPV virus. These 9 types account for 90% of cervical cancers.” Bill Chesnut M.D.

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· Why Adults Should Get the HPV Vaccine
· When Should Adults Get the HPV Vaccine?
· Are There Any Adults Who Should Not Receive the HPV Vaccine?
· What Are the HPV Vaccine Ingredients?
· What Are the Risks and Side Effects of the HPV Vaccine?
Human papillomavirus (HPV) is the virus that causes cervical cancer in women and genital warts in men and women. The HPV vaccine effectively prevents infection with the HPV types responsible for most cervical cancers and can also prevent genital warts. HPV vaccination is most effective during childhood or adolescence, but adults can also benefit from the HPV vaccine.

Why Adults Should Get the HPV Vaccine

HPV infection is extremely common; most sexually active people will be infected with HPV at some point in life. HPV infection usually causes no symptoms, but can cause genital warts and anal cancer in both women and men. HPV can also cause throat cancer.

In women, HPV infection can cause cells in the cervix to grow abnormally. In a small fraction of women, these HPV-induced changes will develop into cervical cancer. About 12,000 women are diagnosed with cervical cancer each year and about 4,000 women die from the condition.

The HPV vaccine prevents infection by the HPV types responsible for most cervical cancers. There are three available forms of the HPV vaccine:

Cervarix: Prevents infection by HPV-16 and HPV-18. These two HPV types cause 70% of all cervical cancers. It is used for the prevention of cervical cancer and precancers.
Gardasil: Prevents infection by HPV-16, HPV-18, and also HPV-6 and HPV-11, the two HPV types that cause 90% of genital warts. It is used to prevent cancers and precancers of the cervix, vulva, vagina, anus, penis, and throat.
Gardasil 9: Prevents infection by the same HPV types as Gardasil, plus HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58. Collectively, these types are implicated in 90% of cervical cancers.
All HPV vaccines are extremely effective at preventing infection by the HPV types they cover. Getting the HPV vaccine reduces a woman’s risk of cervical cancer and precancerous growths substantially. Men cannot develop cervical cancer, but the HPV vaccine may prevent genital warts, anal cancer, and the spread of HPV to sexual partners. Gardasiland, Gardasil 9 are approved for males ages 9 through 26.

The HPV vaccine does not treat or cure an HPV infection in women or men who are already infected by one of these HPV types.

When Should Adults Get the HPV Vaccine?

The CDC recommends that all women ages 26 years and younger receive three doses of the HPV vaccine. The CDC recommends that all men ages 21 years and younger receive three doses of the HPV vaccine. It is an option for all men, but is recommended for men who have sex with men or who have a compromised immune system (including HIV) who are ages 26 and younger.

CDC guidelines recommend the three doses of the HPV vaccine should be given as follows:

First dose: ideally at ages 11 or 12
Second dose: one to two months after the first dose
Third dose: six months after the first dose
Some adults may have received doses of the HPV vaccine in childhood or adolescence. All three doses should be given to get the most protection from HPV infection. Re-vaccination in adulthood is recommended if the vaccination schedule was not completed.

Are There Any Adults Who Should Not Receive the HPV Vaccine?

Certain people should not get the HPV vaccine or should wait before getting it:

Anyone who has had a life-threatening allergic reaction to a previous dose of the HPV vaccine
Anyone who has had a previous life-threatening allergic reaction to an ingredient in the HPV vaccine
Pregnant women
Anyone with a moderate or severe illness; people who feel mildly ill may still receive the HPV vaccine.
The HPV vaccine is not known to be harmful to pregnant women or their babies. However, until more information is known, pregnant women are advised not to receive the HPV vaccine. Women who are breastfeeding can safely receive the HPV vaccine.

The HPV vaccine’s safety and effectiveness have not yet been studied in adults older than age 26. Until that information is available, the HPV vaccine is not recommended for adults older than age 26.

What Are the HPV Vaccine Ingredients?

The HPV vaccine contains no viruses and is not made from human papillomavirus. The active ingredients in the HPV vaccine are proteins that are similar to those found in the human papillomavirus. Genetically modified bacteria produce the proteins, which are then purified and mixed into a sterile, water-based solution.

What Are the Risks and Side Effects of the HPV Vaccine?

In clinical trials and in real-world use, the HPV vaccine appears to be very safe. More than 40 million doses of the vaccine — mostly Gardasil, which was approved in 2006 — have been given in the U.S. Cervarix was approved in 2009 and Gardasil 9 was approved in 2014.

From 2006 to 2014, there were about 25,000 reports to the government of HPV vaccine side effects. Over 90% of these were classified as nonserious. The most common side effects of the HPV vaccine are minor:

About one in 10 people will have a mild fever after the injection.
About one person in 30 will get itching at the injection site.
About one in 60 people will experience a moderate fever.
These symptoms go away quickly without treatment. Other mild-to-moderate side effects resulting from the HPV vaccine include:

Nausea
Fainting
Headache
Arm pain

Severe side effects, or adverse events, are uncommonly reported and have included:

Blood clots
Seizures
Guillain-Barre syndrome
Chronic inflammatory demyelinating polyneuropathy
Systemic exertion intolerance disease (formerly called chronic fatigue syndrome)
Death
Government, academic, and other public health investigators could not identify the HPV vaccine as the cause of any severe adverse event. There were 117 deaths as of September 2015, none of which could be directly tied to the HPV vaccine. The conclusion of public health investigators was that the HPV vaccine was unlikely to be the cause of these events. Such events occur at a certain rate in any group of tens of millions of people. The vaccination before each adverse event seemed to be a simple coincidence.

PPIs prematurely age cells that line the inside of blood vessels.

“The side effects of long term Omeprazole, Nexium and its related drugs, called PPIs, is alarming. On May 10 a report described PPI drugs being associated with central nervous system dysfunction. Avoid PPI drugs and use Zantac and its class of medications.” Bill Chesnut, MD

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PPIs prematurely age cells that line the inside of blood vessels, study suggests. AMA Wire __May 11, 2016.

The Houston Chronicle (5/10, Hawryluk) reports that research suggests “proton pump inhibitors prematurely age the cells that line the inside of blood vessels, making them less resistant to blockages that can cause heart attacks and strokes.” The findings were published in Circulation Research.

HealthDay (5/10, Thompson) reports that the findings, from “lab tests,” may “explain why other studies have shown increased risk of heart disease in people who use” PPIs, “said study senior author Dr. John Cooke.”

________________________________________________________________

CIRCULATION RESEARCH_American Heart Association.

Proton Pump Inhibitors Accelerate Endothelial Senescence

Abstract
Rationale: Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, now available for long-term use without medical supervision. Recent reports suggest that PPI use is associated with cardiovascular, renal and neurological morbidity.

Objective: To study the long-term effect of PPIs on endothelial dysfunction and senescence and investigate the mechanism involved in PPI induced vascular dysfunction.

Methods and Results: Chronic exposure to PPIs impaired endothelial function and accelerated human endothelial senescence by reducing telomere length.

Conclusions: Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal and neurological morbidity and mortality.

Silent heart attacks make up 45% of all heart attacks.

“The Wake Forest School of Medicine studied > 9,000 people. The paper is Race and Sex Differences in the Incidence and Prognostic Significance of Silent Myocardial Infarction in the Atherosclerosis Risk in Communities (ARIC) Study. The important finding is not about sex and race differences but that 45% of heart attacks (myocardial infarction) are not clinically documented meaning not causing enough symptoms to cause medical attention. The silent myocardial infarction (SMI) incidence was surprising. The SMI was detected by EKG changes in people who had no symptoms of ever having a heart attack. The study was over eight years. The combined total of heart attacks was 7.4% of the studied group. A heart healthy life style is even more important with this information.” Bill Chesnut, MD
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Silent heart attacks make up 45% of all heart attacks, study suggests

TIME (5/16, Alter) reports that research suggests “silent heart attacks, which have no symptoms but still involve a loss of blood flow to the heart, make up 45% of all heart attacks and triple the chances of dying from heart disease.” The findings were published in Circulation.

NBC News (5/16, Fox, Powers) reports on its website that investigators “looked at the medical records of 9,500 middle-aged men and women taking part in a heart disease risk study.” The researchers found that “nine years into the study, 317 of the volunteers had ‘silent’ heart attacks and 386 had heart attacks that were noticed right away.”

On its website, CBS News (5/16, Marcus) reports that the researchers also found that “found that silent heart attacks were more common in men – but more likely to cause death in women.”

CNN (5/16, Kounang) reports that the study indicated “having a silent heart attack increased the chances of dying from heart disease threefold and increased chances of dying from any cause by 34%.”

Surgical options correct the cause of reflux

“The treatment options for sufferers of GERD are increasing. The surgery to correct refractory cases is becoming less major with a faster recovery. Also the incidences of side effects of the Proton Pump Inhibitor medications is increasing, now including central nervous system problems. I included this here because the improvements in treatments is not widely known.” Bill Chesnut, MD

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Surgical options correct the cause of reflux

The surgical options attack the actual cause of the problem – the dysfunction of the lower esophageal sphincter (LES). Each attempts to correct the problem rather than covering it up with PPIs. I will summarize every available alternative and encourage further investigation of each.

Nissen fundoplication

Considered the “gold standard” of surgical antireflux therapy is the laparoscopic Nissen Fundoplication. This procedure restores the function of the LES by wrapping a portion of the upper stomach loosely around the lower esophagus. It is performed under general anesthesia using minimally invasive techniques. Five 1/2-1 inch incisions are required and it necessitates a one-day hospital stay. A “soft food” diet is typically suggested initially with gradual resumption to a normal diet taking 6-12 weeks. Although this is not a difficult procedure, it has its nuances and must be performed by a surgeon experienced in this procedure for optimal results. This operation stops the reflux in approximately 80-85% of patients, returning the pH test to normal.

This procedure eliminates the need for PPIs in most patients with the most well performed studies showing approximately 90% of surgical patients do not require those medications. Approximately the same number indicate that they are satisfied with the procedure in the 5-10 year time frame.

Even though the satisfaction rate is great, there are side effects with this procedure including swallowing difficulty (2-5% of patients), bloating and diarrhea to various degrees (10-20% of patients), and the inability to belch and vomit (30% of patients). These side effects seem to vary with the experience of the surgeon. In good hands, this is a proven, effective alternative to PPI therapy. Susan should also understand that a Nissen procedure can repair even the largest of hiatal hernias.

LINX Reflux Management System

Last year, the FDA approved a new procedure called the LINX Reflux Management System. This procedure places a magnetic bracelet around the lower esophagus to “augment” the failed LES. This is a minimally invasive technique and is typically completed in about 30 minutes. A regular diet and full activity is immediately resumed and the reflux is stopped approximately 70% of the time without the typical side effects associated with a Nissen procedure, except that a small number of recipients have difficulty swallowing.

The latest study of 100 patients showed 85% have eliminated PPIs after 3-5 years and 94% would recommend the procedure to a friend. Only 2% had swallowing difficulty, which was corrected with a simple non-surgical dilation (gentle stretching of the esophagus.) This procedure is available at a limited number of select locations in the US.

Incisionless procedures

Two procedures are available that are performed orally and do not require incisions. The TIF procedure, also know as the Esophyx procedure, and the Stretta procedure are both performed through the mouth. Since no incision is required, many individuals find this an attractive feature for both procedures. These two procedures do not have a predictable effect on eliminating reflux and studies have conflicted on the ability of patients to eliminate their PPI use. Many recipients report an improved “quality of life” although there is a concern that the elimination of reflux is not predictable and PPIs may be required long-term for some. In the only 10-year study on Stretta available, only 23% remained off PPIs at 10 years. As is the case with Nissen procedures, the skill set of the surgeon is an important factor is successful outcomes. Also, according to several surgeons, patient selection is an important variable as well.

Weigh your options

As discussed, there are alternatives to long-term PPI use to GERD. These treatment alternatives are becoming more attractive and receiving more interest today as consumers become more aware of the potential for negative long-term side affects from PPIs. For Susan, the best non-medical procedure seems to be the laparoscopic Nissen fundoplication since she describes a hiatal hernia. If it is greater than 3 cm in size, Nissen is the only recommended choice. If the hernia is less than 3cm, all of these procedures are options.

Hormone replacement therapy, HRT, in early menopause may slow progression of cardiovascular disease.

“Hormone Replacement therapy in early menopause is important to decrease the bone loss following menopause. I have posted several articles on this website related to osteoporosis. Post-menopausal women not taking hormone replacement lose 60% of their total bone mass between menopause and 60 years of age.

Now another benefit is reported. The study below shows slowing of atherosclerosis by taking hormone replacement.

It is important to know what replacement is most safe. Also know the safety advantages of vaginal or topical HRT versus oral hormone placement. The metabolism is different when taking a medical orally than transcutaneous. Vaginal HRT with estriol elevates estriol a little and transiently if it elevates blood levels at all.

Testosterone is another hormone loss in menopause. Its involvement in bone loss and atherosclerosis has not been as extensively tested. The research available that I found does not report a significant risk of testosterone replacement to keep the normal pre-menopausal blood level.

This finding is so important in my view that I posted the abstract of the original article just below the announcement in the popular press.

If you know women in the age group to be peri-menopausal please tell them the news.” Bill Chesnut, MD

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Starting HRT in early menopause may slow progression of cardiovascular disease, study indicates

The Wall Street Journal (3/30, Beck, Subscription Publication) reports the findings of a 643-patient study published in the New England Journal of Medicine study add to the evidence that beginning hormone replacement therapy (HRT) in early menopause may be protective against cardiovascular disease.

The NPR (3/30, Bichell) “Shots” blog reports that in the study, investigators “directly tested the effect of starting hormone therapy within the first six years after menopause, versus the effect of starting 10 years or more after menopause.” After five years, researchers found that “women who started hormones within six years of menopause had artery walls that thickened a little more slowly than the women on the placebo, whereas the extra estrogen did not seem to slow thickening in the group that started the hormone therapy later.”

ORIGINAL ARTICLE

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

Howard N. Hodis, M.D., Wendy J. Mack, Ph.D., Victor W. Henderson, M.D., Donna Shoupe, M.D., Matthew J. Budoff, M.D., Juliana Hwang-Levine, Pharm.D., Yanjie Li, M.D., Mei Feng, M.D., Laurie Dustin, M.S., Naoko Kono, M.P.H., Frank Z. Stanczyk, Ph.D., Robert H. Selzer, M.S., and Stanley P. Azen, Ph.D., for the ELITE Research Group*

N Engl J Med 2016; 374:1221-1231March 31, 2016DOI: 10.1056/NEJMoa1505241

BACKGROUND

Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.

METHODS

A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima–media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen.

RESULTS

After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum.

CONCLUSIONS

Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.)

Specific genes associated with marijuana addiction

“A genetic factor in cannabis dependence severity is important for the public to know. Look into the paragraph of Design, Setting, and Participants to appreciate the quality of this research. A 90% association of this genetic factor with another psychiatric condition or addiction is stunning.

The first paragraph is an announcement in the popular media. I looked up the original article and publish that article’s abstract below the horizontal line.” Bill Chesnut, MD

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Researchers identify specific genes associated with marijuana addiction

TIME (3/30, Szalavitz) reports that “specific genes associated with marijuana addiction have been identified – and some of them are also linked to increased risk for depression and schizophrenia.” Researchers arrived at this conclusion after studying “the genes of nearly 15,000 people from three different groups.” The study’s findings may “help explain why 90% of people with marijuana addictions also suffer from another psychiatric condition or addiction.” The study was published online in JAMA Psychiatry.

Below is the abstract of that original research publication March 30, 2016.

Online First >

Original Investigation | March 30, 2016

Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks ONLINE FIRST

Richard Sherva, PhD¹; Qian Wang, MS²; Henry Kranzler, MD^3,4; Hongyu Zhao, PhD^2,5,6,7; Ryan Koesterer, MS¹; Aryeh Herman, PsyD⁸; Lindsay A. Farrer, PhD^1,9,10,11,12; Joel Gelernter, MD^7,8,13,14

JAMA Psychiatry. Published online March 30, 2016. doi:10.1001/jamapsychiatry.2016.0036

ABSTRACT

Importance Cannabis dependence (CAD) is a serious problem worldwide and is of growing importance in the United States because cannabis is increasingly available legally. Although genetic factors contribute substantially to CAD risk, at present no well-established specific genetic risk factors for CAD have been elucidated.

Objective To report findings for DSM-IV CAD criteria from association analyses performed in large cohorts of African American and European American participants from 3 studies of substance use disorder genetics.

Design, Setting, and Participants This genome-wide association study for DSM-IV CAD criterion count was performed in 3 independent substance dependence cohorts (the Yale-Penn Study, Study of Addiction: Genetics and Environment [SAGE], and International Consortium on the Genetics of Heroin Dependence [ICGHD]). A referral sample and volunteers recruited in the community and from substance abuse treatment centers included 6000 African American and 8754 European American participants, including some from small families. Participants from the Yale-Penn Study were recruited from 2000 to 2013. Data were collected for the SAGE trial from 1990 to 2007 and for the ICGHD from 2004 to 2009. Data were analyzed from January 2, 2013, to November 9, 2015.

Main Outcomes and Measures Criterion count for DSM-IV CAD.

Results Among the 14 754 participants, 7879 were male, 6875 were female, and the mean (SD) age was 39.2 (10.2) years. Three independent regions with genome-wide significant single-nucleotide polymorphism associations were identified, considering the largest possible sample. These included rs143244591 (β = 0.54,P = 4.32 × 10⁻¹⁰ for the meta-analysis) in novel antisense transcript RP11-206M11.7;rs146091982 (β = 0.54,P = 1.33 × 10⁻⁹ for the meta-analysis) in the solute carrier family 35 member G1 gene (SLC35G1); andrs77378271 (β = 0.29, P = 2.13 × 10⁻⁸ for the meta-analysis) in the CUB and Sushi multiple domains 1 gene (CSMD1). Also noted was evidence of genome-level pleiotropy between CAD and major depressive disorder and for an association with single-nucleotide polymorphisms in genes associated with schizophrenia risk. Several of the genes identified have functions related to neuronal calcium homeostasis or central nervous system development.

Conclusions and Relevance These results are the first, to our knowledge, to identify specific CAD risk alleles and potential genetic factors contributing to the comorbidity of CAD with major depression and schizophrenia.

Reversible Stomach Tube May Be an Alternative to Bariatric Surgery

“You have got to read this. Using a stomach feeding tube to treat obesity? How about that.The treatments for medical conditions in severe obesity are not ideal. The surgery is complicated. This website explains the details of the types of gastrointestinal operations developed to try to reverse obesity safely. https://asmbs.org/resources/story-of-obesity-surgery This simple idea of inserting a tube to drain the stomach appears to produce excellent results with minimal complications. The report of a new procedure was April 11, 2016 at a conference of Interventional Radiologists. It is not FDA approved yet. Expect it will be approved and cost effective. This is great news for obese patients with severe degeneration in their backs, hips, knees and feet.” Bill Chesnut, MD

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Reversible Gastrostomy Tube May Be an Alternative to Bariatric Surgery: Presented at SIR

Created 04/11/2016 – 16:21

By Lorraine L. Janeczko

VANCOUVER — April 11, 2016 — A tube running from the stomach directly out the body through the abdomen may be an alternative to bariatric surgery for obese patients, according to research presented here at the 41st Annual Scientific Meeting of the Society of Interventional Radiology (SIR).

“This is a safe, easy, relatively low-risk procedure that can be removed when desired and can result in high weight loss,” said Shelby Sullivan, MD, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri. “Right now, very few patients are optimally treated for obesity, and we need to be able to treat more patients with additional tools like this device that have lower risk than bariatric surgery but that achieves higher weight loss than lifestyle therapy alone.”

The AspireAssist Aspiration Therapy System consists of a percutaneous gastrostomy tube with one end placed inside the stomach and the other end connected to a port outside the abdomen, as well as a removable siphon that facilitates aspiration. The device allowed each patient to expel roughly 30% of their most recent meal before it was digested. Although the study was planned to run for 1 year, 12 patients chose to remain implanted for 3 years.

To evaluate the weight-loss efficacy and safety of the endoscopically placed device, lead author Stephen Solomon, MD, Department of Radiology, Cornell University, New York, New York, and colleagues enrolled 25 obese patients with a mean body mass index (BMI) of 39.8 kg/m2 in a pilot study at Blekinge County Hospital, Karlskrona, Sweden, between July and September 2012.

Of these, 22 patients completed 1 year, 15 completed 2 years, and 12 completed 3 years. For the 12 who completed 3 years, the mean weight loss was 26 kg with a mean excess weight loss of 58%. The mean weight loss at the end of years 1, 2, and 3 was 48% (19 kg), 46% (18 kg), and 45% excess weight loss (19 kg), respectively, on an intent-to-treat basis using the last observation carried forward method.

“The misconception is that you can eat anything and then aspirate it,” explained Dr. Sullivan. “In reality, patients must eat less than before. The food particles have to be smaller than 5 mm in size to fit through the tube. To get good aspiration, patients have to chew their food until it disintegrates in their mouth.”

“People not only get tired of chewing and stop eating earlier in the meal than before, they eat more slowly, can sense feeling full and push away from the meal,” he said. “The patients also need to drink a lot of water with their meal to create a slurry that can be aspirated. This reduces the amount of food they can fit into their stomach.”

The device is available on a limited basis in Europe and select additional regions. It is not approved by the US Food and Drug Administration (FDA) yet.

One-third of advanced-melanoma patients given nivolumab in study are alive five years after starting treatment

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Reversible Gastrostomy Tube May Be an Alternative to Bariatric Surgery: Presented at SIR

Created 04/11/2016 – 16:21

By Lorraine L. Janeczko

The device is available on a limited basis in Europe and select additional regions. It is not approved by the US Food and Drug Administration (FDA) yet.

The Accidental Deadly Drug Prescription

“There are many publications the medical world about opioid medications. Managing chronic pain without risking accidental death is hard. This article looks at anther much less known risk of opioid medications. The grave risk for some is combining an opioid with a benzodiazepine drug such as Xanax. This is a commentary in the Wall Street Journal. Dr. Wen shows you the difficulty in practicing the best medicine, being effective and keeps risks as low as possible. If you friends who take pain pills, tell them about the benzodiazepine class of drugs, all of their brand names. ” Bill Chesnut, MD

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The Accidental Deadly Drug Prescription. Many doctors are unaware that a drug like Valium or Xanax, taken with an opioid, could be fatal. By LEANA S. WEN,MD_______March 30, 2016

My patient was a college student brought into the emergency room after a minor car accident. Although CT scans showed no spinal fractures, he had severe neck pain and spasms. Instinctively, I prescribed Percocet for pain and Valium for muscle spasms. But I didn’t know then what I know now: These two drugs, when taken together, could interact and cost him his life.

Opioids—including prescriptions such as Percocet and OxyContin, as well as the illicit form, heroin—are under increased scrutiny. The number of Americans dying from an opioid overdose has quadrupled over the past decade, according to the Centers for Disease Control and Prevention. This week President Obama joined health officials and advocates to raise awareness of this growing epidemic. Clinicians and the public, however, are often unaware of the threat posed by opioid interaction with another frequently prescribed drug.

Benzodiazepines, known to most Americans as Xanax or Valium, typically treat anxiety or insomnia. But when combined with opioids, as they often are, they can suppress the instinct to breathe, increase sleepiness and cause death. In 2010, one in three unintentional overdose deaths in the U.S. from prescription opioids also involved benzodiazepines, according to the National Vital Statistics System. Maryland Department of Health data show more than 70% of deaths in the state associated with benzodiazepines also involved prescription opioids.

Despite this danger, doctors prescribe both drugs at increasing rates. The CDC reported that in 2012 there were over 259 million prescriptions of opioids in the U.S.—more than one for every adult. That year there were nearly 40 benzodiazepine prescriptions for every 100 Americans. Hospital admissions for patients with combined addiction to opioids and benzodiazepines have increased by 569% over 10 years, according to anotherfederal study.

Why do doctors continue to prescribe this deadly combination? In part, because that is what they are taught. When I was in medical school in the early 2000s, I learned to treat muscle pain and spasms with both opioids and benzodiazepines, so I routinely prescribed them together. A 2015 study published in the journal Pain Medicine found that one in three patients with chronic pain on opioids was also on benzodiazepines. Just as I acted on instinct with my ER patient, doctors prescribe medications based on habit.

Most overdose-education campaigns focus exclusively on the opioid epidemic, in part because there is an easy-to-use antidote available, naloxone. In Baltimore, we have increased its availability by allowing all 620,000 residents to obtain a naloxone prescription—no questions asked. Last year, we conducted over 8,000 targeted trainings, going to high-risk areas like jails, bus shelters and public markets to demonstrate use of this lifesaving medication.

Likewise, education for physicians has focused on increasing monitoring of opioid prescriptions, rather than on decreasing their use with benzodiazepines. But with mounting scientific and epidemiological evidence about this deadly combination, doctors must adjust their patterns. Shouldn’t they already know that combining these drugs is dangerous? Unfortunately, the figures suggest they don’t.

Last month, I co-led a coalition of over 40 city health-commissioners and state health-directors who sent a petition urging the Food and Drug Administration to require a “black-box warning”—the FDA’s strongest risk communication—any time that opioids and benzodiazepines are prescribed together. Such a warning would sound the alarm about the danger of taking these drugs at the same time. Thousands of health officials, academics, researchers, physicians and citizens signed our petition.

Studies show that black-box warnings change how physicians prescribe potentially dangerous medications. In the mid-2000s, a black-box warning was issued for an antidepressant associated with suicide in youth. This resulted in a 22% drop in prescriptions, according to a study in the American Journal of Psychiatry. Physicians listened to the warning and changed their practices.

The FDA recently proposed a black-box warning on opioids. It is a welcome move: 44 Americans die every day from prescription opioid overdose. Yet, while one-third of those deaths were associated with an unintentional combination with benzodiazepines, the FDA’s new warning doesn’t mention the dangers of combining the drugs.

When I look back at my practice, I wonder how many deaths my colleagues and I might have caused inadvertently—and how many we could have prevented if we had known the potential dangers sooner. It’s a harrowing thought that should spur physicians to change their prescribing practices and patients to look inside their medicine cabinets.

Dr. Wen is an emergency physician and the health commissioner for the city of Baltimore.

Breast Cancer Reoperation Rate Is Nearly Halved When MRI Findings Are

“Using bilateral MRI when planning surgery of breast cancer improves results in 1,926 patients.” Bill Chesnut, MD

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Reoperation Rate Is Nearly Halved When MRI Findings Are Included in Planned Surgical Treatment DG News_March 8, 2016 By Jenny Powers

VIENNA, Austria — March 8, 2016 — A comparison between two cohorts of patients who did and did not receive magnetic resonance imaging (MRI) in addition to mammography or ultrasound before breast cancer surgery revealed that MRI detected additional contralateral lesions and provided information that significantly altered surgical plans, researchers reported here on March 3 at the 2016 Annual European Congress of Radiology (ECR).

The study included women with newly-diagnosed breast cancer who were not candidates for neoadjuvant therapy. Surgical treatment was pre-planned for all women in the study based on mammography and or ultrasound, but one cohort received an MRI prior to surgery and one group did not.

To date 4,295 women have been enrolled in the ongoing study. The current analysis included data from 1,926 women aged 18 to 80 years, of whom 972 received MRI and 954 did not.

“The cohorts were not homogenous and significant differences in age and breast density were seen in the groups,” noted Giovanni Di Leo, MD, Radiology Unit, IRCCS Policlinico, Milan, Italy.

Patient age was 56 years in the MRI group versus 61 years in the non-MRI group and ACR breast density was 12% versus 18%, respectively (P < .001 for both).

The mastectomy rate was significantly higher in patients having MRI in addition to mammography or ultrasound (20.1% vs 14.0%; P < .001).

Pre-planned breast conserving surgery based upon MRI results was unchanged in 74% of women in the MRI cohort, altered to less extensive surgical treatment in 13%, and to a broader surgical treatment in 13% of women.

The rate of MRI-detected new contralateral cancers was (2%).

Importantly, the number of subsequent surgeries was significantly reduced in patients receiving MRI. The reoperation rate for positive margins was 7% in the MRI group compared with 13% in the non-MRI group (P < .001).

“The order for an MRI was made by a radiologist in 67% of the cases and by a surgeon in 40% of cases,” said Dr. Di Leo. “More mastectomies had already been planned on the basis of mammography or ultrasound in patients receiving MRI; this higher rate is due to a selection bias. One could say MRI is a confirmation tool for mastectomy.”

The European Congress of Radiology is sponsored by the European Society for Radiology.

Insufficient maternal D3 during pregnancy may increase the risk of MS in offspring.

“Know your Vitamin D3 total blood test level! Don’t assume it is normal only because you live a normal life. My view is that every adult should have one “screening” blood test of their Vitamin D3. Its easy, cheap and risk free to correct. The Mayo Clinic in their wellness division thinks there patients do best if there Vit D3 test (250hydroxy Vitmain D3 total) is around 5- ng/dl. I have seen many orthopedic problems resolve when correcting a Vitamin D deficiency.” Bill Chesnut, MD.

To go back to New Health News: https://billchesnutmd.com/new-health-news

JAMA NEUROLOGY

Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort _ Original Investigation | March 07, 2016 Kassandra L. Munger, ScD¹; Julia Åivo, MD²; Kira Hongell, MD²; Merja Soilu-Hänninen, MD²; Heljä-Marja Surcel, PhD³; Alberto Ascherio, MD, DrPH^1,4

Importance Vitamin D has been associated with a decreased risk of multiple sclerosis (MS) in adulthood; however, some, but not all, previous studies have suggested that in utero vitamin D exposure may be a risk factor for MS later in life.

Objective To examine whether serum 25-hydroxyvitamin D (25[OH]D) levels in early pregnancy are associated with risk of MS in offspring.

Design, Setting, and Participants Prospective, nested case-control study in the Finnish Maternity Cohort conducted in May 2011. We identified 193 individuals with a diagnosis of MS before December 31, 2009, whose mothers are in the Finnish Maternity Cohort and had an available serum sample from the pregnancy with the affected child. We matched 176 cases with 326 controls on region of birth in Finland, date of maternal serum sample collection, date of mother’s birth, and date of child’s birth.

Main Outcomes and Measures Maternal serum 25(OH)D levels were measured using a chemiluminescence assay. The risk of MS among offspring and association with maternal 25(OH)D levels were the main outcomes. Conditional logistic regression was used and further adjusted for sex of the child, gestational age at the time of sample collection, and season of sample collection to estimate the relative risks and 95% CIs.

Results Of the 193 cases in the study, 163 were female. Of the 331 controls in the study, 218 were female. Seventy percent of serum samples were collected during the first trimester of pregnancy. The mean (SD) maternal vitamin D levels were in the insufficient vitamin D range, but higher in maternal control than case samples (15.02 [6.41] ng/mL vs 13.86 [5.49] ng/mL [to convert to nanomoles per liter, multiply by 2.496]). Maternal vitamin D deficiency (25[OH]D levels <12.02 ng/mL) during early pregnancy was associated with a nearly 2-fold increased risk of MS in the offspring (relative risk, 1.90; 95% CI, 1.20-3.01; P = .006) compared with women who did not have deficient 25(OH)D levels. There was no statistically significant association between the risk of MS and increasing serum 25(OH)D levels (P = .12).

Conclusions and Relevance Insufficient maternal 25(OH)D during pregnancy may increase the risk of MS in offspring.

Postmenopausal bone loss is a major concern for orthopedic surgeons.

“Postmenopausal bone loss is a major concern for orthopedic surgeons. We know that 25% of a woman’s total bone mass before menopause is lost by age 65. There are a high emphasis and research trying to deliver methods to restore that bone loss or stop further loss. Some women have striking amounts of bone loss and pathological fractures. Fractures occurring from a standing height are called a “fragility fractures” whether it is the wrist, kneecap, hip or spine. A fragility fracture is an alarm to begin studies of bone mass and metabolism. The odds are high of another fragility fracture occurring without medical intervention.

Developing methods to restore bone loss years after menopause is the late side of this problem. The early smart approach in medicine is to prevent the bone loss by methods in peri-menopausal women. Many studies were done relating to the safety of using some form of estrogen early in menopause. There are increased risks starting estrogen five years after menopause. These may be lessened by using Estriol, the weakest form of estrogen and avoiding giving the medication orally. By avoiding the oral administration, you avoid the “first pass” metabolism that affects the hormone. Using estriol intravaginally has increasing research experience to show it does not cause hyperplasia of the endometrium. The data is increasing that it decreases urinary incontinence by its effect on the urethra and vaginal tissue. There have not been extensive studies of estriol vaginally yet. There is a reason to combine testosterone with the estriol vaginally for muscle strength and the bone strengthening result of getting more physical activity.

Many practitioners are not aware of the most recent developments in my experience. My bigger concern is that so many people I have seen as patients were not aware they need to research safe hormone replacement early in menopause. I posted 14 articles related to postmenopausal hormone deprivation as a “category of posts” on the homepage.” Bill Chesnut, MD.

To go back to New Health News: https://billchesnutmd.com/new-health-news

Anti-Mullerian Hormone and Prediction of Trans-Menopausal Bone Loss The Endocrine Society 1016 meeting _ a presentation. Friday, April 1, 2016

Arun S Karlamangla^*¹, Albert Shieh¹, Sherri-Ann M Burnett-Bowie², Elaine W. Yu², Gail A Greendale¹, Patrick M. Sluss², Deborah Martin³and Joel S Finkelstein²
¹University of California, Los Angeles, CA, ²Massachusetts General Hospital, Boston, MA, ³University of Pittsburgh, Pittsburgh, PA

The menopause transition (MT) in women is a period of bone loss, with the most rapid declines occurring in a 3-year period bracketing the final menstrual period (FMP). This period of rapid bone loss has been called the trans-menopause, and the rate of BMD decline over this period varies substantially between women (1). Circulating levels of Anti-Mullerian Hormone (AMH) made by ovarian granulosa cells also decline as women progress through the MT (2). We hypothesized that serum levels of AMH in women early in the MT will predict the rate of bone loss over the trans-menopause. We tested this hypothesis using data from The Study of Women’s Health Across the Nation, a 7-site, multi-ethnic study of the MT. At baseline, participants had to be 42 to 52 years old, pre- or early peri-menopausal, have an intact uterus with 1 or 2 ovaries, and not be taking exogenous sex steroid hormones. Enrollment began in 1996 and women were asked to return annually. At each visit, blood was collected between 8:00 and 10:00 AM after a 12-hour fast, during the early follicular phase (cycle days 2–5) whenever possible, and serum was stored at -80F. In all women who had a natural (non-surgical) MT and a dateable FMP, serum level of AMH was measured from frozen blood samples using a new high-sensitivity monoclonal ELISA with a detection limit of 2 pg/mL (Pico AMH, Ansh Labs, Webster, TX). BMD [bone mass density] in the lumbar spine and femoral neck was measured annually in 5 of the 7 study sites. In 474 women who had AMH and BMD measurements between 2 and 4 years before the FMP, had a 2^nd BMD measurement 3-4 years later, and had not taken any medications that affect bone prior to the 2^nd BMD measurement, we examined the ability of AMH level to predict the annualized rate of BMD decline between the two visits (% decline per year). AMH inter-quartile range was [11,146] pg/mL. Median rate of BMD decline was 1.3% per year in the spine and 1.0% per year in the femoral neck. Adjusted for age, BMI, smoking, race/ethnicity, and study site, in multivariable linear regression, each 75% (or four-fold) decrement in AMH level was associated with 0.15% per year faster decline in spine BMD (p<0.001) and 0.13% per year faster decline in femoral neck BMD (p=0.005). These associations persisted even after additional adjustment for time from FMP and serum levels of estradiol and FSH. In multivariable logistic regression, adjusted for age, BMI, smoking, race/ethnicity, and study site, each four-fold decrement in AMH level was also associated with 18% increase in the odds of faster-than-median decline in spine BMD (p=0.02) and 17% increase in the odds of faster-than-median decline in femoral neck BMD (p=0.02). These findings suggest that serum levels of AMH in women going through the MT can indeed predict the rate of trans-menopausal bone loss, and help identify the women at risk of most loss. AMH levels appear to provide information about the rate of bone loss beyond that provided by serum levels of estradiol and FSH.

(1) Greendale GA et al., JBMR 2012; 27: 111-8. (2) Sowers MFR et al., JCEM 2008; 93: 3478-83.

What’s New in Adult Reconstructive Knee Surgery

“This is a review article from JBJS, a specialty update. These updates are yearly, cover the new developments and often mention consensus opinions. The comments about tibial osteotomy surgery for knee arthritis are important. In the national consensus, an osteotomy is one surgical choice that is not a knee replacement. The surgical technique for tibial osteotomy is significantly improved by the instruments developed by Arthrex, Naples Florida, in my opinion, based on personally performing many tibial osteotomies. If you need arthritis knee surgery, find a surgeon who offers tibial osteotomy as a choice.” Bill Chesnut, MD.

To return to New Health News for more news: https://billchesnutmd.com/new-health-news

What’s New in Adult Reconstructive Knee Surgery: Level I and II Studies. OrthoBuzz Feb 26, 2016.

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in January 20, 2016 Specialty Update on adult reconstructive knee surgery:

Nonsurgical Management and Osteotomy

A Cochrane database review found that land-based therapeutic exercise programs were modestly beneficial to patients with knee arthritis. Individualized programs were more effective than exercise classes or home-exercise programs.1
A study comparing intravenous administration of tanezumab versus naproxen and placebo in patients with hip and knee osteoarthritis found that tanezumab effectively relieved pain and improved function at week 16.2
A comparison of platelet-rich plasma (PRP) injections and hyaluronic acid (HA) injections found both treatments to be equally effective in improving knee function and reducing symptoms as measured by the IKDC subjective score.3
A study comparing opening-wedge and closing-wedge high tibial osteotomy found that among patients who did not go on to conversion to TKA, there were no between-group differences in clinical or radiographic outcomes at six years of follow-up.

Implants, Instrumentation, and Technique

A comparison of highly cross-linked and conventional polyethylene in posterior cruciate-substituting TKA found no differences in pain, function, and radiographic outcomes at a mean of 5.9 years.
A randomized study of 140 patients that compared the use of patient-specific instrumentation (PSI) and conventional instrumentation found no differences in clinical, operative, and radiographic results.4
In a randomized trial of 200 patients, the use of electromagnetic computer navigation resulted ininsignificantly fewer outliers from the target alignment, compared with the use of conventional instrumentation. There were no between-group differences in clinical outcomes.5
In a prospective randomized trial, the use of computer-assisted navigation during TKA resulted in lower systemic embolic loads, compared with TKA performed using conventional intramedullary instrumentation.
A randomized controlled trial comparing kinematically and mechanically aligned TKA found that kinematic alignment with patient-specific guides provided better pain relief and restored better function and range of motion than mechanical alignment using conventional instruments.6
A randomized study of selective patellar resurfacing in 327 knees followed for a mean of 7.8 years found higher satisfaction among patients with a resurfaced patella.7

Pain and Blood Management: A randomized controlled trial comparing femoral and adductor canal blocks found that adductor canal blocks decreased time to discharge readiness without an increase in narcotic consumption.8

A trial comparing periarticular injections (PAIs) of liposomal bupivacaine with conventional bupivacaine PAI found no between-group differences in VAS pain scores 72 hours postoperatively orin patient narcotic consumption.9
A double-blinded randomized trial comparing topical versus intravenous administration of tranexamic acid found no significant differences in estimated blood loss or complications.

Rehabilitation and Complications

A randomized trial of 205 post-TKA patients found no differences in WOMAC scores for pain, function, and stiffness in groups thatreceivedtelerehabilitation or face-to-face home therapy.
A randomized trial found that Kinesio Taping helped reduce postoperative pain and swelling and improved knee extension during early postoperative rehabilitation.10
A trial comparing oral edoxaban and subcutaneous enoxaparin for post-TKA thromboprophylaxis found that edoxaban wasthe more effective agent. The incidence of bleeding events was similar in both groups.11

Return to New Health News, https://billchesnutmd.com/new-health-news/

Gastric Bypass Surgery in Patients Aged Older Than 35 Associated With Improved Survival

“Great news here that gastric bypass surgery helps in adults aged 35 and older. This post from the AMA News joins similar results in orthopedic research including the benefits of gastric bypass surgery before knee replacement arthroplasty. I added the emphasis in the last paragraph highlighting the good news.” Bill Chesnut, MD

Gastric Bypass Surgery in Patients Aged Older Than 35 Associated With Improved Survival February 10, 2016

Lance E. Davidson, Ph.D., of Brigham Young University, Provo, Utah, and colleagues examined whether gastric bypass surgery is equally effective in reducing mortality in groups undergoing surgery at different ages. The study was published online by JAMA Surgery.

Bariatric surgery is effective in reducing all-cause and cause-specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known. For this study, all-cause and cause-specific mortality rates were estimated from a cohort within 4 categories defined by age at surgery; younger than 35 years, 35 through 44 years, 45 through 54 years, and 55 through 74 years. A cohort of 7,925 patients undergoing gastric bypass surgery and 7,925 group-matched, severely obese individuals who did not undergo surgery were identified through driver license records.

The authors found that gastric bypass surgery was associated with improved long-term survival for all patients undergoing surgery at ages older than 35 years. The lack of mortality benefit for those younger than 35 years was primarily derived from a significantly higher number of externally caused deaths, particularly among women. “Importantly, this study implies that gastric bypass surgery is protective against mortality even for patients who undergo surgery at an older age. Gastric bypass surgery also reduces the age-related increase in mortality risk compared with severely obese individuals who do not undergo surgery.”

To read the full article and a related commentary by Malcolm K. Robinson, M.D., of Harvard Medical School and Brigham and Women’s Hospital, Boston, please visit the For The Media website.

SOURCE: JAMA Surgery

Effects of Testosterone Treatment in Older Men

“Hormone replacement has many benefits. As an orthopedic surgery specialty hormone deprivation is a concern for commonly causing a loss of bone mass and density. In women, it is established that 25% of the total bone mass is lost from menopause to age 60 years. The same occurs in men with hyperandrogenism, low testosterone; I do not have the frequency (incidence rate) nor the average amount of bone loss in men. There are many other benefits besides increased sexual function. The effects of the various methods of replacing testosterone are not addressed here. In addition to testosterone gels, there is injectable testosterone cypionate and an implantable deposit of testosterone showing promising early results. My point with this post is there are more medical reasons to consider hormone replacement in addition to changing sexual activity. A simple Internet search can lead you to the right data; especially look for statements from a specialty society such as the American Academy of Orthopaedic Surgeons.” Bill Chesnut, MD.

Effects of Testosterone Treatment in Older Men

Peter J. Snyder, M.D., Shalender Bhasin, M.D., Glenn R. Cunningham, M.D., Alvin M. Matsumoto, M.D., Alisa J. Stephens-Shields, Ph.D., Jane A. Cauley, Dr.P.H., Thomas M. Gill, M.D., Elizabeth Barrett-Connor, M.D., Ronald S. Swerdloff, M.D., Christina Wang, M.D., Kristine E. Ensrud, M.D., M.P.H., Cora E. Lewis, M.D., M.S.P.H., John T. Farrar, M.D., Ph.D., David Cella, Ph.D., Raymond C. Rosen, Ph.D., Marco Pahor, M.D., Jill P. Crandall, M.D., Mark E. Molitch, M.D., Denise Cifelli, M.S., Darlene Dougar, M.P.H., Laura Fluharty, M.P.H., Susan M. Resnick, Ph.D., Thomas W. Storer, Ph.D., Stephen Anton, Ph.D., Shehzad Basaria, M.D., Susan J. Diem, M.D., M.P.H., Xiaoling Hou, M.S., Emile R. Mohler, III, M.D., J. Kellogg Parsons, M.D., M.H.S., Nanette K. Wenger, M.D., Bret Zeldow, M.S., J. Richard Landis, Ph.D., and Susan S. Ellenberg, Ph.D. for the Testosterone Trials Investigators

N Engl J Med 2016; 374:611-624February 18, 2016DOI: 10.1056/NEJMoa1506119

BACKGROUND

Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.

METHODS

We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials — the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants.

RESULTS

Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy–Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups.

CONCLUSIONS

In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.)

Clinical Practice Guideline for Post-Surgical Pain Management

“Significant gains in surgery pain control are available now. They are the use of long established modalities now used safely together. The importance of the original research is to have the dosage chart for each of the modalities. The term multimodal therapy is used for the general area of surgery pain control. Multimodal therapy improves the quality of recovery, shortens complication rates and readmission rates. It also increases costs. Being aware and having a source may become helpful for someone who is having surgery. They should discuss these facts with their anesthesiologist and their surgeon.” Bill Chesnut, MD

American Pain Society Publishes Clinical Practice Guideline for Post-Surgical Pain Management February 17, 2016

CHICAGO — February 17, 2016 — The American Pain Society (APS) has released a new evidence-based clinical practice guideline with 32 recommendations to help clinicians achieve optimal pain management following surgery.

According to numerous studies, the majority of surgical patients receive inadequate pain relief, which can heighten the risk for prolonged post-surgical pain, mood disorders, and physical impairment.

“The intent of the guideline is to provide evidence-based recommendations for better management of postoperative pain, and the target audience is all clinicians who manage pain resulting from surgery,” said lead author Roger Chou, MD, Oregon Evidence-based Practice Center.

Dr. Chou said the key recommendation in the guideline, based on high-quality evidence, is wider use of a variety of analgesic medications and techniques.

“The guideline strongly advises use of multimodal anesthesia that target different mechanisms of actions in the peripheral and central nervous systems,” he said. “Randomized trials have shown that multimodal anesthesia involving simultaneous use of combinations of several medications — acting on different pain receptors or administered through different techniques — are associated with superior pain relief and decreased opioid consumption compared with use of a single medication administered by one technique.”

Dr. Chou added that evidence also indicates that non-pharmacological therapies, such as cognitive behavioral therapies and transcutaneous elective nerve stimulation, can be effective adjuncts to pharmacological therapies.

Written by a 23-member expert panel representing anesthesia, pain management, surgery, nursing, and other medical specialties, the APS guideline — published in the Journal of Pain — is based on the panel’s review of more than 6,500 scientific abstracts and primary studies.

The guideline’s 32 recommendations are rated as strong, moderate or weak based on scientific evidence cited as high, moderate or low quality. The recommendations are based on the premise that optimal pain management begins in the preoperative period and should be based on assessment of the patient and development of individual care plans for the surgical procedure involved.

Three other recommendations in the APS guideline are graded strong with high-quality evidence. They are:
• Adults and children can be given acetaminophen and/or non-steroidal anti-inflammatory drugs as part of multimodal analgesia for management of postoperative pain.
• Clinicians should consider surgical site-specific peripheral regional anesthetic techniques with proven efficacy in adults and children for certain procedures.
• Spinal analgesia is appropriate for major thoracic and abdominal procedures, particularly in patients at risk for cardiac and pulmonary complications or prolonged intestinal distress.

The APS Guideline offers 11 other strong recommendations, based on moderate or weak evidence. They include:
• Clinicians should provide patient and family-centered, individually tailored education to patients and caregivers about treatment options for postoperative pain.
• Oral administration of opioids is preferred to intravenous administration for post-operative analgesia.
• Intravenous patient-controlled analgesia (PCA) can be used when parenteral administration of analgesics is required.
• Clinicians should consider giving preoperative doses of celecoxib in appropriate adult patients.
• Gabapentin and pregabalin can be considered for multimodal postoperative analgesia. The medications are associated with lower opioid requirements after surgery.
• Surgical facilities should provide clinicians with access to a pain specialist for patients with inadequately controlled postoperative pain.

The APS postoperative pain management guideline was endorsed by the American Society for Regional Anesthesia.

SOURCE: American Pain Society

HPV infections falling among young women

“Great news here that needs to be widely disseminated in my view. We should encourage the use of the HPV vaccine in children 11-12 years of age. This post is from AMA News and links to the original article. I posted the original article abstract below for your information. As parents, it is easy to forget this information. Secondly it may be difficult to explain to the child it a necessity to prevent cancers in young adults. Important.” Bill Chesnut, MD

HPV infections falling among young women, study shows

USA Today (2/22, Painter) reports a study published in Pediatrics suggests that “thanks to a vaccination program that began a decade ago, fewer U.S. women are entering adulthood infected with” HPV. This study “is the first to show falling levels of dangerous strains of the” virus “among women in their early 20s.”

The Pittsburgh Post-Gazette (2/22, Sostek) reports that the study found “girls between 14 and 19 years old saw infection rates on the four types of HPV covered by the Gardasil vaccine fall 64 percent from the rate prior to the vaccine’s introduction — from 11.5 percent in 2003-2006 to 4.3 percent between 2009 and 2012.” Meanwhile, “in women ages 20 to 24, prevalence of the infection declined 34 percent in those years, from 18.5 percent to 12.1 percent.”

Pediatrics ___________________________________

March 2016

Prevalence of HPV After Introduction of the Vaccination Program in the United States

Lauri E. Markowitz, Gui Liu, Susan Hariri, Martin Steinau, Eileen F. Dunne, Elizabeth R. Unger

BACKGROUND: Since mid-2006, human papillomavirus (HPV) vaccination has been recommended for females aged 11 to 12 years and through 26 years if not previously vaccinated.

METHODS: HPV DNA prevalence was analyzed in cervicovaginal specimens from females aged 14 to 34 years in NHANES in the prevaccine era (2003–2006) and 4 years of the vaccine era (2009–2012) according to age group. Prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV-6, -11, -16, and -18) and other HPV type categories were compared between eras. Prevalence among sexually active females aged 14 to 24 years was also analyzed according to vaccination history.

RESULTS: Between the prevacccine and vaccine eras, 4vHPV type prevalence declined from 11.5% to 4.3% (adjusted prevalence ratio [aPR]: 0.36 [95% confidence interval (CI): 0.21–0.61]) among females aged 14 to 19 years and from 18.5% to 12.1% (aPR: 0.66 [95% CI: 0.47–0.93]) among females aged 20 to 24 years. There was no decrease in 4vHPV type prevalence in older age groups. Within the vaccine era, among sexually active females aged 14 to 24 years, 4vHPV type prevalence was lower in vaccinated (≥1 dose) compared with unvaccinated females: 2.1% vs 16.9% (aPR: 0.11 [95% CI: 0.05–0.24]). There were no statistically significant changes in other HPV type categories that indicate cross-protection.

CONCLUSIONS: Within 6 years of vaccine introduction, there was a 64% decrease in 4vHPV type prevalence among females aged 14 to 19 years and a 34% decrease among those aged 20 to 24 years. This finding extends previous observations of population impact in the United States and demonstrates the first national evidence of impact among females in their 20s.

Accepted October 30, 2015.

Neanderthal DNA may predispose some people to nicotine addiction, mood disorders

“This is a study of 28,000 people by evolutionary geneticists. It helps understand that some of the maladies we have some from “bad code.” The original study is here for more details: http://science.sciencemag.org/content/351/6274/737.full .” Bill Chesnut, MD

Nicotine addiction and mood disorders associated with Neanderthal Genes. “Neanderthal DNA may predispose some people to nicotine addiction, mood disorders.”

The Washington Post (2/11, Nutt) reports in “Speaking of Science” that the “first-ever study directly comparing Neanderthal DNA to the human genome confirmed a wide range of health-related associations.” Lead author John Capra, PhD, an evolutionary geneticist at Vanderbilt University, said, “Our main finding is that Neanderthal DNA does influence clinical traits in modern humans.” The article explains that “snippets of Neanderthal DNA contribute to the contemporary risk for myriad ills, including heart attack, nicotine addiction, and mood disorders as well as incontinence, foot calluses and precancerous skin lesions.”

The Wall Street Journal (2/11, Long, Subscription Publication) reports that to arrive at these conclusions, the researchers compared electronic health records from 28,000 people of European ancestry with genomes from fossilized Neanderthal bones. The study was published online in the journal Science.

Exposure to flashes of light the night before traveling may help reduce jet lag, study suggests

“This is fascinating to read in the original article. It has a good discussion of sleep patterns. “Temporal integration of light flashes by the human circadian system“ http://www.jci.org/articles/view/82306 Bill Chesnut, MDsystem.”

Exposure to flashes of light the night before traveling may help reduce jet lag, study suggests

The Wall Street Journal (2/8, Reddy, Subscription Publication) reports that research published in the Journal of Clinical Investigation suggests exposing someone to flashes of light the night prior to traveling may help reduce the likelihood that he or she will experience jet lag.

CNN (2/8, Grinberg) reports that in the study, participants slept in a “lab, where some were exposed to continuous light for an hour and others were exposed to a sequence of flashes of various frequencies for an hour.” Investigators found that “exposing people to two millisecond flashes of light, similar to a camera flash, every 10 seconds elicited two hours of change in circadian timing.”

STAT (2/8, Swetlitz) reports that “a couple of individuals in this group saw a shift in their internal clock of up to three hours.” Comparatively, study participants who were “exposed to continuous light for the hour experienced an average change to their circadian clocks of only about 30 minutes.”

Health and Diet

Study offers clues to genetic abnormality of C4 genes associated with schizophrenia

“The January 2016 AMA newsletter reports DNA testing showing an abnormality of the C4 genes associated with a much higher incidence of schizophrenia. Other recent publications report improvements in schizophrenia if treatment began early and involve the family.” Bill Chesnut, MD

Study offers clues to biology behind schizophrenia

On its front page, the New York Times (1/27, A1, Carey, Subscription Publication) reports that a new study published online Jan. 27 in Nature takes “a significant step toward understanding the cause of schizophrenia,” providing “the first rigorously tested insight into the biology behind any common psychiatric disorder.”

In “Science Now,” the Los Angeles Times (1/27, Healy) reports, “After conducting genetic tests on nearly 65,000 people, the scientists followed a trail of clues to a group of genes in the” major histocompatibility complex (MHC) “called C4 genes.” Investigators “found that people with certain variants of C4 genes had unusually high odds of developing schizophrenia, even in the absence of other genetic risks.” By demonstrating “a link between C4 and synaptic pruning,” the study “builds on theories that the over-editing of brain connections in late adolescence might be ‘a contributing cause’ of schizophrenia.”

The Washington Post (1/27, Nutt) reports in “Speaking of Science” that in people “with schizophrenia, a variation in a single position in the DNA sequence marks too many synapses for removal and that pruning goes out of control,” resulting in “an abnormal loss of gray matter.” According to the Post, the “study offers a new approach to schizophrenia research, which has been largely stagnant for decades.”

AMA News 1.28.16

Ultimate cause of Alzheimer’s may be fungal, cadaver study suggests

“This new finding is remarkable in many ways. Has anyone heard about this work in the media? Pub Med includes a 2014 article in J. Alzheimers Disease of fungus in Alzheimer’s brains. The abstract says:

To our knowledge, these findings represent the first evidence that fungal infection is detectable in brain samples from Alzheimer’s disease patients. The possibility that this may represent a risk factor or may contribute to the etiological cause of Alzheimer’s disease is discussed. http://www.ncbi.nlm.nih.gov/pubmed/24614898

A Google review today finds the study in GIZMODO October 26, 2015. http://gizmodo.com/new-study-suggests-alzheimers-is-associated-with-brain-1738788855

Clearly this is astoundingly good news by opening a possible treatment for Alzheimer’s. I am eager to follow this topic.” Bill Chesnut, MD

Ultimate cause of Alzheimer’s may be fungal, cadaver study suggests

The Economist (10/23) reports that a study published online Oct. 15 in the journal Scientific Reports suggests that “the ultimate cause of Alzheimer’s is fungal.” Researchers arrived at this conclusion after examining “brain tissue from 25 cadavers, 14 of which belonged to people who had had Alzheimer’s disease when alive.” The study authors now “think a clinical trial of anti-fungal drugs is the next logical step.

From the abstract of the study: The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

Pisa, D. et al. Different Brain Regions are Infected with Fungi in Alzheimer’s Disease. Sci. Rep. 5, 15015; doi: 10.1038/srep15015 (2015).”

Wear and Osteolysis of Highly Crosslinked Polyethylene at 10 to 14 Years

“How long will the plastic liner in total hips last? You won’t believe how good this stuff has become.” Bill Chesnut, MD

Wear and Osteolysis of Highly Crosslinked Polyethylene at 10 to 14 Years: Predicts 345.8333333333333 years of wear available for 28 mm cup. Paul F. Lachiewicz MD, Elizabeth S. Soileau BSN, John M. Martell MD

Background. Highly crosslinked polyethylene (XLPE) was introduced to decrease periprosthetic osteolysis related to polyethylene wear, a major reason for revision of total hip arthroplasty. However, there are few reports of wear and osteolysis at 10 years postoperatively.

Questions/purposes. (1) What are the linear and volumetric wear rates of XLPE at 10 to 14 years? (2) What is the relationship among linear wear, volumetric wear, and femoral head size? (3) What proportion of hips developed osteolysis and was there a relationship between osteolysis and femoral head size or polyethylene wear?

Methods. We evaluated a previously reported cohort of 84 hips (72 patients) with one design of an uncemented acetabular component and one electron beam 10-kGy irradiated and remelted XLPE at a mean followup of 11 years (range, 10–14 years). The choice of femoral head size was based on several factors, including the outer diameter size of the acetabular component implanted, the perceived risk of dislocation (including the history of alcohol abuse and patient age), and liner availability from the manufacturer. The femoral head sizes used were 26 mm in 10 hips (12%), 28 mm in 31 hips (37%), 32 mm in 31 hips (37%), 36 mm in eight hips (10%), and 40 mm in four hips (5%). Measurements of linear and volumetric wear were performed in one experienced laboratory by the Martell method and analyzed using the first-to-last method. Standard radiographs, with additional Judet views, were used to detect periprosthetic osteolysis. Statistical analysis of wear and osteolysis compared with head size was performed.

Results. For the entire cohort, the median linear wear rate as 0.024 mm/year (95% confidence interval [CI], 0.016–0.030) and the median volumetric wear rate was 12.19 mm/year (95% CI, 6.6–15.7). With the numbers available, we found no association between femoral head size and linear wear rate. However, larger femoral heads were associated with more volumetric wear; 36/40-mm femoral heads had higher volumetric wear (median 26.1; 95% CI, 11.3–47.1) than did 26-mm heads (median 3.1; 95% CI, 0.7–12.3), 28-mm heads (median 12.3; 95% CI, 3.0–19.3), and 32-mm heads (median 12.9; 95% CI, 6.6–16.8; p = 0.02). Small osteolytic lesions were noted in 12 hips (14%), but with the numbers available, there was no association with head size or volumetric wear rates.

Conclusions. This uncemented acetabular component and this particular XLPE had low rates of linear and volumetric wear. Small osteolytic lesions were noted at 10 to 14 years but were not related to femoral head size or linear or volumetric wear rates. We recommend additional longer-term clinical followup studies and perhaps alternative imaging studies of patients with XLPE and osteolysis.

CRR: Feb1, 2016