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Vol. 3 No. 43


‘Stark’ maternal-adiposity results highlight
importance of pre-conception weight loss

KING GEORGE, VA. – Research indicating that adult children of mothers with pre-pregnancy overweight or obesity have higher body mass index (BMI) and greater odds of adult obesity than adult children of normal-weight mothers is another wake-up call on the importance of weight loss.

It also provides a strong motivation for overweight mothers-to-be, says one obesity management expert, to act on behalf of their unborn children even when they are less inclined to help themselves.

The study published in November in Obesity examined the relationship between pre-natal, maternal weight and the progressive BMI of offspring throughout adulthood during a 40-year follow-up. Children of mothers with pre-natal overweight or obesity demonstrated greater BMI throughout adulthood with a more rapid consistent weight acceleration in early and mid-adulthood---something that was not seen in children of mothers with normal pre-conception weight.  This held true even in women with obesity who lost weight prior to conception.

The findings from this study associating pre-natal overweight and obesity to offspring adiposity doesn’t surprise nurse practitioner (NP) Christine Kessler, founder of Metabolic Medicine Associates in King George, Va., Kessler, faculty co-chair of the Metabolic & Endocrine Disease Summit (MEDS), notes that “for many years there has been accumulating evidence that suggest increased obesity risk may begin in utero due to fetal exposure to maternal adiposity, although the biological mechanism for this is not clearly understood.  This large longitudinal study, adjusted for inherited, genetic pre-disposition and lifestyle factors, offers greater support for the causal relationship of maternal weight and offspring obesity.”

Based on Framingham Heart Study data and funded by the National Institutes of Health, the study urges lifestyle interventions, which Kessler fully supports.

“This study,” says Kessler, “provides us with the stark results of excess maternal adiposity on a child’s obesity risk and long-term weight trajectory, compared to normal weight mothers.  It also highlights the importance of weight reduction prior to conception focusing on life-long, evidenced-based lifestyle interventions that promote healthy weight loss and maintenance, which includes individualized plans for nutrition, sleep, and physical-activity levels.  Bariatric surgery may also be an option for those contemplating pregnancy. Although prescription weight-loss medications are useful, none are currently approved for use in pregnancy.”

“Fertility,” she adds “also improves with weight loss, which can be another motivator. We need to inform our child-bearing women about the perils of overweight and obesity with regard to the ability to conceive, and the increased life-long risk of un-healthy adiposity in their children. Women aren’t always aware that their own weight can contribute to a two-and-a-half to five-fold risk of increased obesity for their offspring. This is huge.”

Kessler also stresses that NPs and physician assistants (PAs) “have a great opportunity to positively affect a mother’s health and that of her offspring with regard to the life-long trajectory of weight issues and associated complications. We can’t change genetics,” she admits, “but we can help educate and motivate women to adapt pre-conception, weight-loss lifestyle changes, armed with information about the disease of obesity and its impact on their children. Doing so will reap great rewards for both mother and child with a positive heath impact that will last long into the future.”

“To effectively provide weight loss interventions,” she concludes, “providers should be knowledgeable about the chronic disease of obesity and its treatment options. Both the American Association of Nurse Practitioners (AANP) and the American Association of Physician Assistants (AAPA) offer online obesity-education programs. Obesity-medicine guidelines can also be found online, including a thorough one offered by the American Association of Clinical Endocrinologists (AACE). It’s past time to help these mother and babies at risk.”

CITATION: Isabelle Schoppa, Asya Lyass, et. al. Association of Maternal Prepregnancy with Offspring Adiposity Throughout Adulthood Over 37 Years of Follow-up. Obesity (Silver Spring). First published: 25 November 2018.


Research on the risk of adult-onset asthma
suggests a greater non-genetic factor role

CHICAGO – Genetic risk factors for adult-onset asthma are largely a subset of the genetic risk for childhood-onset asthma but with overall smaller effects, according to a recent study suggesting a greater role for non-genetic risk factors in adult-onset asthma.

The study published in April in The Lancet  indicates that, combined with gene-expression and tissue-enrichment patterns, the establishment of disease in children is driven more by dysregulated allergy and epithelial-barrier function genes, while the cause of adult-onset asthma is more lung-centered and environmentally-determined---but with immune-mediated mechanisms driving disease progression in both children and adults.

Authors of the research include Milton Pividori and Nathan Schoettler, The University of Chicago.

The study, funded by the National Institutes of Health, involved genome-wide and transcriptome-wide studies, using data from the UK Biobank, in individuals with asthma, including adults with childhood-onset asthma (onset before 12-years-of-age), adults with adult-onset asthma (onset between 26-and-65 years of age), and adults without asthma (controls; aged older than 38 years).

The authors conducted genome-wide association studies (GWAS) for childhood-onset asthma and adult-onset asthma, each compared with shared controls, and for age of asthma onset in all asthma cases.

Enrichment studies determined the tissues in which genes at GWAS loci were most highly expressed; PrediXcan, a transcriptome-wide gene-based test, was used to identify candidate-risk genes.

Of 376,358 British white individuals from the UK Biobank, the researchers included 37,846 with self-reports of doctor-diagnosed asthma: 9,433 adults with childhood-onset asthma; 21,564 adults with adult-onset asthma; and an additional 6,849 young adults with asthma with onset between 12-and-25 years of age.

For the first and second GWAS analyses, 318,237 individuals older than 38 without asthma were used as controls. The authors detected 61 independent asthma loci: 23 were childhood-onset specific, one was adult-onset specific, and 37 were shared; 19 loci were associated with age of asthma onset.

CITATION: Milton Pividori, Ph.D., Nathan Schoettler, MD, et. al. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies. The Lancet. Volume 7, Issue 6, P509-522, June 1, 2019. Published: April 26, 2019.


Investigation into HRQOL suggested prior
to fracture in assessment of osteoporosis

KINGSTON, ONTARIO – A study involving data from more than 7,000 subjects provides evidence of substantially-reduced health-related quality of life (HRQOL) in women and men with self-reported and/or bone-mineral density (BMD)-confirmed osteoporosis, even in the absence of fragility fracture.

The study published in May in Osteoporosis International indicates that HRQOL should be thoroughly investigated even prior to fracture in order to develop appropriate interventions for all stages of the disease.

Its authors---including Wilma M. Hopman, Kingston Health Sciences Centre, Kingston, Ontario---noted that fragility fractures have a detrimental effect on HRQOL of osteoporosis patients, and that less is known about the association between HRQOL and osteoporosis in the absence of fracture.

The study included responses to the Canadian Multicentre Osteoporosis Study by participants who completed the SF-36, a detailed health questionnaire. The researchers reported on the results of participants aged 50-and-older, with 10-year follow-up.

Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multi-variable linear-regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information.

Baseline data were available for 5,266 women and 2,112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, especially in the physically-oriented domains, than those without osteoporosis.

A similar-but-attenuated pattern was evident for men. After 10-year follow-up (2,797 women and 1,023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time.

CITATION: W.M. Hopman, C. Berger, et. al. Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study. Osteoporosis International. Pages 1-10. First Online: 08 May 2019.


Joint model for prediction of CKD progression
to ESKD said no better than traditional approach

NIJMEGEN, NETHERLANDS – Recent research indicates that in studies in which outcome is rare and follow-up data highly complete, the joint model for early prediction of chronic kidney disease (CKD) progression to end-stage kidney disease (ESKD) doesn’t offer improvement in predictive performance over more traditional approaches such as a survival model with time-varying estimated glomerular filtration rate (eGFR), or a model with eGFR slope.

Authors of the study published in May in PLOS ONE include Jan A. J. G. van den Brand, Radboud University Medical Center, Nijmegen, Netherlands, and Tjeerd M.H. Dijkstra, University Tubingen, Tubingen, Germany.

Early predictions of CKD progression to ESKD use Cox models including baseline eGFR only. Alternative approaches include a Cox model that includes eGFR slope determined over a baseline period of time, a Cox model with time-varying GFR, or a joint-modeling approach.
All models in the prospective-cohort study included age, sex, eGFR, and albuminuria, known prognostic markers for ESKD.

The researchers trained the models on data on 505 subjects and 55 ESKD events, and determined discrimination and calibration for each model at two years follow-up for a prediction horizon of two years in a test of 1,385 subjects and 72 events.

They benchmarked the predictive performance against the Kidney Failure Risk Equation (KFRE).

The C-statistic for the KFRE was 0.94. Performance was similar for the Cox model with time-varying eGFR, eGFR, and the joint model. The Cox model with eGFR slope showed the best calibration.

The authors recommend a straightforward survival model with GFR slope, estimated from an ordinary least squares (OLS) regression model, when the outcome of interest is rare and follow-up is highly complete.

In these cases, bias due to informative drop-out is unlikely to have a substantial impact on predictive performance. In practice, this means that a physician can use the most recent GFR value (or series of values when calculating a slope eGFR) to fill out a risk calculator.

CITATION: Jan A. J. G. van den Brand, Tjeerd M. H. Dijkstra, et. al. Predicting kidney failure from longitudinal kidney function trajectory: A comparison of models. PLOS ONE. May 9, 2019.


Self-discipline, self-control, management
touted as tools against depression, diabetes

KUWAIT CITY, KUWAIT – Recent research indicates that battling depression in diabetes patients is crucial to control of blood-glucose and metabolic-disorder complications, and that patients can benefit from increased self-discipline, self-control, and disease management.

The study published in May in Diabetes Research and Clinical Practice focuses on the association between fasting during the month of Ramadan---a period of self-discipline, self-control, and spirituality---and depression.

Its authors---including Ebaa Al-Ozairi and Manar M. AlAwadhi, Kuwait University, Safat, Kuwait City, Kuwait---utilized data from 463 participants, which was collected at three time points. A paired t-test was used to examine the difference between PHQ-9 scores and Psychometric Properties of the Problem Areas in Diabetes (PAID) scores before- and-after Ramadan to measure depression.

A multi-variable regression adjusted for potential confounders was used to study the association between fasting and depression.

The difference in PHQ-9 scores before and after Ramadan was -3.5 points, and the difference in PAID scores before-and-after Ramadan was -5.02 points.

For every one-year increase in diabetes diagnosis, PHQ-9 scores decreased by 0.09 after Ramadan. Female participants had decreases of 1.17 more points in PHQ-9 scores than male participants.

CITATION: Ebaa Al-Ozairi, Manar M. AlAwadhi, et. al. A prospective study of the effect of fasting during the month of Ramadan on depression and diabetes distress in people with type 2 diabetes. Diabetes Research and Clinical Practice. Published online: May 17, 2019. Accepted: May 9, 2019. Received: February 14, 2019.


Bone health for kidney-disease patients
is addressed in Clinician Reviews article

An article posted in June in Clinician Reviews takes on the topic of using dual-energy X-ray absorptiometry (DXA) and bisphosphonates in patients with chronic kidney disease (CKD) and end-stage renal disease. Written by Rebecca Grillo, PA-C, RD, LD/N, the piece points out that mineral-and-bone disorder (MBD) is a common complication for kidney-disease patients, and that CKD-MBD is a systemic disorder that encompasses abnormalities in mineral metabolism, skeletal health, and soft-tissue calcifications. The article also reports that, before starting treatment for CKD-associated osteoporosis, regardless of stage, it is important to manage vitamin D deficiency, hyperphosphatemia, and hyperparathyroidism. The story can be accessed at



Vol. 3 No. 42

Role of health-care providers called key
to improving lives of asthmatic children

NAMPA, IDAHO – Research indicating that home-based environmental-control interventions don’t reduce asthma emergency department (ED) re-visits for children with poorly-controlled asthma and second-hand smoke (SHS) exposure doesn’t surprise one asthma expert, who points to special challenges faced by asthmatic children.

Brian K. Bizik, MS, PA-C, physician assistant, Terry Reilly Health Center, Nampa, Idaho, says the study published in January in Pediatric Pulmonology underscores the fact that “asthma is different for children.”

Bizik, past president, Association of PAs in Allergy, Asthma and Immunology, and a faculty member of Cardiovascular, Allergy, & Respiratory Summit (CARPS), says asthma among children “can be severe, and make for bigger challenges.”

He explains that, “for one thing, there are infections: The number-one cause of asthma flare-ups are infections. Children are exposed to these more, at school, and playing with their friends. There is a spike in asthma-related incidents caused by infections early in the school year, in the first two weeks.”

“Children are germ factories,” he continues. “They share toys, and they also have an inability to communicate and describe what they are feeling, that, for instance, they have been wheezing. And inhalers are hard for them to use; there is a learning curve. There are factors that are hard for them to control, like whether their parents smoke.”

And while the study points to the dangers of SHS exposure for asthmatic children, which Bizik says parents are well-aware of, behavior often lags far behind good intentions.

“All the patients I see who smoke say they are quitting,” says Bizik, “and when I see them a year later, they are quitting again. They know, and understand, that SHS isn’t good for their children. While there is awareness, and understanding, it is still very hard for them to quit.”

He adds that health-care practitioners, including physician assistants (PAs) and nurse practitioners (NPs), can play key roles in turning this around.

“The most effective smoking-cessation tool we have,” he says, “is clear communication about what smoking does to patients, and to those around them. If someone comes in for a sprained ankle, we ask about smoking. NPs and PAs are on the front line of urgent care: We have opportunities to tell people they need to stop smoking.”

Bizik praised the study, but cautions that unless health-care professionals are pro-active, its lessons will remain unlearned, let alone acted upon.

The researchers, he notes, “used a very-well thought out plan that included allergy blood tests and treatment, traps for cockroaches and mice as well, as intensive parental education.  Despite this, however, most parents did not stop smoking during the three-year study. The study also showed that when patients over-used their rescue inhalers, the risk of an ED visit increased greatly.  Even with all these well thought-out interventions, this study showed just how difficult it is to change home environments.”,

Bizik stresses that, “in terms of turning this around, we can suggest well-studied interventions like the use of air purifiers and SHS avoidance, but in the end, the best tracking tool we have is the use, and over-use, of rescue inhalers”

He points to the “rule of twos that we try to encourage for our patients. This rule encourages using less than two rescue inhalers in a year, and using a rescue inhaler less than two times per week when not sick. When patients stick to this rule of twos, we know the risk for a visit to the ED is reduced. In the past few years, we have greatly increased our ability to track prescriptions like opiates; we need to move that tracking to asthma rescue inhalers to really make a dent in the ED visits for asthma.”  

Again, education is essential.

“We need to make sure,” he concludes, “that parents realize that asthma is different for children than for adults. Children still die of asthma, even mild asthma. This is a serious, life-threatening disease, nothing to be toyed with. We can make a dent through education and through tracking inhaler use: If an inhaler is used more than twice a week, come in and see me. Maybe there is an infection.”

CITATIONS: Butz AM, Bollinger ME, et. al. Children with poorly controlled asthma: Randomized controlled trial of a home-based environmental control intervention. Pediatric Pulmonology. 2019 Jan. 6.


Assessment of hypertensive population
targets risks of T2D, low blood pressure

PISA, ITALY – Research utilizing a Renal Insufficiency and Cardiovascular Events (RIACE) Italian multi-center study cohort, at variance with the general hypertensive population, indicates that resistant hypertension does not predict death beyond target- organ damage.

Findings in the study published in April in BMC Medicine may be explained by the high mortality risk conferred by type 2 diabetes (T2D) and the low blood-pressure (BP) values observed in controlled-hypertensive patients.

The researchers---including Anna Solini and Giuseppe Penno, University of Pisa, Pisa, Italy---indicate that this may mask risk associated with resistant hypertension, and that less-stringent BP goals may be preferable in high-risk patients with T2D.

The researchers retrieved vital-status information in 2015 for 15,656 of the 15,773 participants enrolled in 2006-to-2008. Based on baseline BP values and treatment, participants were categorized as:

  • normotensive
  • untreated hypertensive
  • controlled hypertensive
  • uncontrolled hypertensive
  • resistant hypertensive

Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan–Meier estimates were highest among resistant hypertension participants, especially those with controlled-resistant hypertension.

As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, but became progressively similar between resistant-and-controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities.

When compared with controlled-resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors, but not for complications/comorbidities.

In individuals with T2D from the RIACE cohort, resistant hypertension did not predict death beyond the increased burden of target-organ damage characterizing this condition.
In addition, risk of death was higher in individuals with controlled-resistant hypertension than in those with uncontrolled resistant hypertension.

CITATION: Anna Solini, Giuseppe Penno, et. al. Is resistant hypertension an independent predictor of all-cause mortality in individuals with type 2 diabetes? A prospective cohort study. BMC Medicine. Received: 3 November 2018. Accepted: 25 March 2019. Published: 25 April 2019.


Research: Baseline-hypertension status
linked to faster kidney-function decline

BALTIMORE – A study assessing nearly 15,000 subjects indicates that, compared to normotension, baseline-hypertension status is associated with faster kidney-function decline over 30-year follow-up in a general-population cohort.

The study, published in April in the American Journal of Kidney Diseases, also indicates that this difference is attenuated among people using anti-hypertensive medications.

Its authors---including Zhi Yu and Casey M. Rebholz, Johns Hopkins Bloomberg School of Public Health, Baltimore---set out to gauge the relationship between hypertension, anti-hypertension medication use, and change in glomerular filtration rate (GFR) over time among patients with preserved GFR.

Their observational study involved 14,854 participants from the Atherosclerosis Risk in Communities (ARIC) Study.

They noted that baseline-hypertension status (1987-to-1989) was categorized according to the 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline as:

  • normal blood pressure
  • elevated blood pressure
  • stage 1 hypertension
  • stage 2 hypertension without medication
  • stage 2 hypertension with medication

Mixed models with random intercepts and random slopes were fit to evaluate the association between baseline-hypertension status and slope of estimated GFR (eGFR).

At baseline, 13.2%, 7.3%, and 19.4% of whites and 15.8%, 14.9%, and 39.9% of African-Americans had stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication.

Compared with those with normal blood pressure, the annual eGFR decline was greater in people with higher blood pressure.

The 30-year predicted probabilities of developing chronic kidney disease CKD) stage G3a+ with normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication among whites were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively, and 55.4%, 62.8%, 60.9%, 76.1%, and 66.6% among African Americans.

CITATION: Zhi Yu, Casey M. Rebholz, et. al. Association Between Hypertension and Kidney Function Decline: The Atherosclerosis Risk in Communities (ARIC) Study. American Journal of Kidney Diseases. Published online: April 25, 2019.


An inherited obesity-susceptibility approach
said to offer clinical-prevention opportunities

CAMBRIDGE, MASS. – Recent research indicates that a new approach to quantify inherited susceptibility to obesity offers new opportunities for clinical prevention and mechanistic assessment.

The study published in April in Cell, whose authors include Amit V. Khera and Mark Chaffin, Broad Institute, Cambridge, Mass., indicates that:

  • a genome-wide polygenic score (GPS) can quantify inherited susceptibility to obesity
  • polygenic-score effect on weight emerges early in life and increases into adulthood
  • effect of polygenic score can be similar to a rare, monogenic-obesity mutation
  • high polygenic score is a strong risk factor for severe obesity and associated diseases

The researchers noted that severe obesity is a rapidly-growing global-health threat, and that, while often attributed to unhealthy lifestyle choices or environmental factors, it is known to be heritable and highly polygenic.

Pointing out that most inherited susceptibility is related to the cumulative effect of many common DNA variants, the authors derived and validated a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and tested this predictor in more than 300,000 subjects, ranging from middle age to birth.

Among middle-aged adults, the researchers observed a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic-score deciles.

In a longitudinal-birth cohort, they note minimal differences in birthweight across score deciles; a significant gradient emerged in early childhood and reached 12 kg by 18 years of age.

They also report that a high GPS for weight and obesity can indicate increased risk of:

  • extreme obesity
  • bariatric surgery
  • coronary disease
  • heart failure
  • mortality

The researchers also conclude that a clear understanding of genetic pre-disposition to obesity may help destigmatize obesity among patients, their health-care providers, and the general public.

CITATION: Khera AV, Chaffin M, et. al. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell. 2019 Apr 18;177(3):587-596.e9.


Study ties socio-economic, marital status
to likelihood of seeking osteoporosis help

SEOUL, SOUTH KOREA – A recent study involving more than 900 female subjects indicates that people with poor knowledge of osteoporosis and those of lower socio-economic status, including the unmarried with low income levels, are less likely to be assessed and treated for the disease.

The study published in April in Osteoporosis International also indicates that individuals with particular osteoporosis risk factors, including smokers and heavy drinkers, are overlooked for diagnosis.

The researchers---including E. S. Lee, who is affiliated with Ewha Womans University, Seoul, South Korea---recommend further study to identify and address the existing barriers and to promote osteoporosis management for women with these risk factors.

They utilized a nationwide online survey involving 926 Korean women over age 50. Their survey included questions addressing three domains:

  • clinical and socio-demographic characteristics
  • reasons for undergoing or avoiding osteoporosis assessment or treatment
  • knowledge of osteoporosis as measured using the modified Korean version of Facts on Osteoporosis Quiz

The highest-ranked reason for undergoing osteoporosis assessment was fear of osteoporotic fracture, while the highest-ranked reason for avoiding osteoporosis assessment was not feeling a need to get tested.

Participants who sought assessment for osteoporosis were older and more likely to be married, and had greater knowledge of osteoporosis than those who did not seek assessment; the two groups were found to be similar in terms of tobacco use and daily alcohol use.

Patients who had been diagnosed with osteoporosis but either did not initiate or discontinued osteoporosis treatment within one year were younger and had lower levels of annual income than those who began and continued treatment.

CITATION: Y.H. Roh, E.S. Lee, et. al. Factors affecting willingness to get assessed and treated for osteoporosis. Osteoporosis International. First online: 03 April 2019.


Clinician Reviews article details the path
to CMV certification for diabetes patients

An article posted in Clinician Reviews addresses the issue of commercial motor vehicle (CMV) drivers with diabetes. Noting that about one-third of CMV drivers have been diagnosed with the disease, the story, written by Shaun Lynch, MS, MMSc, PA-C, Elon University, N.C., reports that U.S. Department of Transportation (DOT) physical exams are mandated for CMV drivers. Federal regulations permit those with stable insulin regimens and properly-controlled diabetes to qualify to operate CMVs. The article can be accessed at



Vol. 3 No. 41

Nitrogen-bisphosphonate research called
‘great avenue’ for osteoporosis progress

SOUTHBURY, CONN. – Research suggesting that nitrogen bisphosphonate (BP) treatment for osteoporosis improves survival irrespective of fracture-risk prevention has been touted by one osteoporosis expert as “a great avenue for progress.”

The study published in January in Osteoporosis International indicates that nitrogen BPs (alendronate, risedronate) but not non-nitrogen BPs (etidronate) are associated with a significant 34% mortality-risk reduction compared to non-treated propensity-score matched controls.

The assessment---a prospective-cohort study of 6,120 participants, male and female, aged 50-and-older---aimed to determine the association between BPs and mortality-risk in participants with or without fractures.

One notable finding is the fact that, despite the availability of effective medications, osteoporosis-treatment rates continue to be low: Fewer-than-30% of women and less-than-20% of men with fragility fractures use validated pharmaceutical treatments.

Southbury, Conn., resident Rick Pope, (PA-C), Department of Rheumatology, Western Connecticut Medical Group, Danbury, Conn.---founder and past president of the Society of Physician Assistants in Rheumatology (SPAR), and faculty member of the Metabolic & Endocrine Disease Summit (MEDS)---attributes this to patients’ attitudes, misunderstandings of side effects, what they have heard from family and friends, and poor interpretations of available information.

“Many older people who experience fractures think it’s bad luck,” notes Pope, “and that they aren’t going to fracture again, and think “I will be very careful.” Also, they don’t want to take another medication, when they already are taking multiple medications.”

Pope adds that publicity in the early 2000’s tying osteonecrosis of the jaw to BPs “caused a falloff in patients taking these medications,” and that, in 2007 and 2008, patients were reading Internet articles indicating that BPs cause fractures, referred to as atypical femoral fractures.

“You have people reading headlines, but not the actual stories---which may be inaccurate---making it hard to institute therapy and adherence. It’s like what we have now, with the misinformation about vaccinations.”

The question, then is how to turn this around.

The answers, says Pope, lie in studies such as the one in Osteoporosis International, as well as the benefits of Fracture Liaison Services, which aims to reduce fracture risk among fragility-fracture risk patients through identification at point-of-fracture treatments.

“It would be an asset to get the message out,” Pope says. “This study is a good first step. There is a desperate need to see an increase in the use of these BPs, for osteoporosis, as well as to promote their potential beneficial effects on the immune system, anti-tumor effect, and endothelial function, which was referenced in the article.

And as the study indicates that, compared to no treatment, nitrogen but not non-nitrogen BPs appear to be associated with better survival, especially among women, Pope stresses the importance of reaching providers, including physician assistants (PAs) and nurse practitioners (NPs), as well as patients, with this information.

He expects the study to be discussed this year by the National Osteoporosis Foundation (NOF), noting that such research “should promote a decrease in mortality. Prevention is important, and when you can reduce death by 34%, and these are statements we need to be making to our patients, which may move the dial in the right direction and be important motivators for our patients.”

“This study,” Pope says, “combines a number of randomized-control trials to suggest that the use of nitrogen-BPs decrease mortality risk and overall mortality. And I would like to see more research.”

This, he says, would include studies focusing on Forteo (teriparatide, targeting men and post-menopausal women with very low-bone density with fractures caused by steroid medication) and Tymlos (abaloparatide, a daily injectable treatment for severe osteoporosis).

“This kind of information,” he concludes, “is a great avenue for progress.”

CITATION: D. Bliuc, T. Tran, et. al. Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study. Osteoporosis International. First online: 03 January 2019. Received: 19 June 2018. Accepted: 11 December 2018.


Moderate muscle strength is associated
with reduced risk of T2D development

AMES, IOWA – Moderate muscular strength, but not upper muscular strength, is associated with reduced risk of type 2 diabetes (T2D) development, independent of estimated cardio-respiratory fitness (CRF), according to research involving more than 4,600 subjects.

Results of a study published in March in Mayo Clinic Proceedings indicate that very high levels of resistance-exercise (RE) training may not be necessary to obtain the considerable health benefits of T2D prevention.

Its authors---including Yuehan Wang and Duck-chul Lee, Iowa State University, Ames, Iowa---recommend additional observational studies with larger sample size and randomized-controlled trials on dose-response relationship of RE and muscular strength with T2D and related chronic diseases.

A total of 4,681 adults aged 20-to-100 without T2D at baseline were included in the current prospective-cohort study. The participants underwent muscular-strength tests and maximal-treadmill exercise tests between Jan. 1, 1981, and Dec. 31, 2006.

Muscular strength was measured by leg-and-bench press and categorized as age group- and sex-specific thirds (lower, middle, and upper) of the combined-strength score.

T2D was defined on the basis of fasting plasma-glucose levels, insulin therapy, or physician diagnoses.

During a mean follow-up of 8.3 years, 229 of the 4,681 patients developed T2D.

Participants with the middle level of muscular strength had a 32% lower risk of T2D development compared with those with the lower level of muscular strength, after adjusting for potential confounders, including estimated CRF.

No significant association between the upper level of muscular strength and incident T2D was observed.

CITATION: Yuehan Wang, BM, Duck-chul Lee, Ph.D., et. al. Association of Muscular Strength and Incidence of Type 2 Diabetes. Mayo Clinic Proceedings. Published online: March 11, 2019.


Study indicates that CKD patients experience
higher rates of pre-operative cardiac disease

SUZHOU, CHINA – A recent study indicates that chronic kidney disease (CKD) patients show higher occurrences of pre-operative cardiac disease than non-CKD patients.

The study published in March in the Journal of Orthopaedic Surgery and Research also indicates that CKD patients have a higher risk of receiving a blood transfusion and being transferred to intensive care units (ICUs) after hip surgery.

Its authors---including Yongqing You, Nanjing Medical University, Suzhou, China, and Yijian Zhang, The First Affiliated Hospital of Soochow University, Suzhou, China---indicate that pre-operative anemia is an independent-risk factor for obtaining a blood transfusion and, therefore, should be focused on during the perioperative period.

Their study enrolled 230 patients (30 with CKD) who underwent hip surgery between 2013-and-2016. Pre-operative, intra-operative, and post-operative data was collected and analyzed between CKD and non-CKD patients.

Logistic regression was used to evaluate the independent-risk factor for post-operative complications.

There were significant differences in the number of people with hypertension, diabetes, coronary-heart disease, smoking habits, anemia, and low hemoglobin levels between CKD and non-CKD patients before surgery.

Receiving a blood transfusion was significantly more common in CKD patients; post-operatively, significant differences were detected in the average number of patients who transferred to the ICU.

Also, differences were found in the quantity of hemoglobin and albumin measured between CKD and non-CKD patients.

Logistic-regression analysis indicated that diabetes, alcohol, and anemia were independent-risk factors for obtaining a blood transfusion, while age, CKD, and osteoporosis were independent-risk factors for ICU transfers.

CITATION: Yongqing You, Yijian Zhang, et. al. Prevalence and risk factors for perioperative complications of CKD patients undergoing elective hip surgery. Journal of Orthopaedic Surgery and Research. Received: 22 August 2018. Accepted: 6 March 2019. Published: 20 March 2019.


Obesity assessment shows connections
between metabolic issues, CVD chances

BOSTON – A study published in March in the Journal of the American Heart Association showed no evidence that metabolically-unhealthy individuals with obesity are at higher risk of cardio-metabolic disease or cardiovascular disease (CVD) than would be expected given the individual associations of those two risk factors with disease states.

Its authors---including Todd R. Sponholtz, Boston University School of Medicine, Boston, and Edwin R. van den Heuvel, Eindhoven University of Technology Eindhoven, The Netherlands---also found that, compared with obesity, being metabolically-unhealthy appeared to be more strongly associated with CVD risk, with the strength of chronic kidney disease (CKD) associations reported as similar.

Obesity was associated with an increased risk of becoming metabolically-unhealthy.

The researchers also observed evidence that body mass index (BMI) variability is associated with higher risk of cardio-metabolic conditions only among individuals without obesity.

While being metabolically-unhealthy increases the risk of obesity, the authors found little evidence that metabolic-health variability was associated with cardio-metabolic risk.

Metabolic-health variability further increased the risk of CVD among metabolically- unhealthy individuals, while BMI variability did not appear to be associated with CVD or CKD.

BMI variability is detrimental to the metabolic health of community‐dwelling adults without obesity. Metabolic-health variability appears primarily to be associated with CVD risk among metabolically-unhealthy individuals.

The authors assessed data involving 3,632 Framingham Heart Study offspring-cohort participants (mean age, 50.8 years; 53.8% women) who were followed-up from 1987-to- 2014.

They defined participants whose variance independent of the mean for a metabolic syndrome-associated measure was in the top quintile as being “variable” for that measure, and investigated the interaction between obesity and metabolic health in their associations with cardio-metabolic disease and CVD.

The researchers also estimated the associations of BMI variability and variable metabolic health with study outcomes within categories of obesity- and metabolic-health status, respectively.

CITATION: Todd R. Sponholtz, Edwin R. van den Heuvel, et. al. Association of Variability in Body Mass Index and Metabolic Health With Cardiometabolic Disease Risk. Journal of the American Heart Association. Originally published 22 March 2019.


Significant positive association reported
between dietary-acid load, hypertension

TEHRAN, IRAN – Recent research indicates a significant positive association between dietary-acid load and hypertension.

The study published in March in Nutrition, Metabolism, & Cardiovascular Diseases also indicates that further studies, especially those with a prospective nature, are needed to confirm these findings.

Its authors---including Mohammad Parohan and Alireza Sadeghi, Tehran University of Medical Sciences, Tehran, Iran---searched online data-bases for relevant publications up to February, 2019, using relevant keywords.

Overall, 14 studies including 306,183 individuals and 62,264 cases of hypertension were included in the meta-analysis.

Combining effect sizes from both prospective- and cross-sectional studies revealed no significant non-linear association between dietary-acid load (based on net-endogenous acid production [NEAP] method) and hypertension.

However, stratified analysis based on study design showed a significant non-linear association between dietary-acid load and hypertension in prospective studies, but not cross-sectional ones.

According to linear dose-response analysis, no significant association was found between dietary-acid load (based on NEAP) and hypertension. In terms of dietary-acid load based on potential renal-acid load (PRAL) method, no significant non-linear association was seen with hypertension.

However, in linear dose-response analysis, a 20-unit increase in PRAL values was associated with 3% increased risk of hypertension.

CITATION: Mohammad Parohan, Alireza Sadeghi, et. al. Dietary acid load and risk of hypertension: a systematic review and dose-response meta-analysis of observational studies. Nutrition, Metabolism, & Cardiovascular Diseases. Published online: March 23, 2019. Accepted: March 15, 2019. Received in revised form: February 12, 2019. Received: August 5, 2018.  


Starting, stopping dialysis addressed
in pair of Clinician Reviews postings

Two recent Clinician Reviews postings address dialysis---both when to start, and when to stop. Tricia Howard, MHS, PA-C, DFAAPA, Georgia Regional Medical Team, Savannah, Ga., replying to a question about beginning dialysis, notes there is no compelling evidence that dialysis initiation based solely on kidney-function measurement improves outcomes, and adds that age and fragility must be considered. Marlene Shaw-Gallagher, PA-C, Michigan Medicine, Ann Arbor, Mich., answering a query about ending dialysis, explains that the prospect of discontinuing dialysis with a diagnosis of end-stage renal disease (ESRD) is very low. She adds that a patient’s underlying etiology influences the chances of recovery, and that those with acute kidney injuries (AKIs) tend to have the best chance. The postings can be accessed at: ;



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