Biomarkers in midlife may predict physical decline years later

Here is a summary of findings published in Circulation:

Clinical Perspective

What Is New?

Lower levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and interleukin-6 in middle-aged adults were independently associated with better physical capability (a key component of healthy aging) up to 9 years later.

Such associations were meaningfully stronger than those observed for conventional risk markers including lipids, blood pressure, and glycemia and were not explained by the onset of cardiovascular and kidney disease or diabetes mellitus.

What Are the Clinical Implications?

Elevated NT-proBNP and interleukin-6 in midlife could help identify (and thereby target) individuals set to have poor physical capability as they age.

Such findings may relate in part to such biomarkers capturing early end-organ damage, or cumulative stressor pathways that lead to physical decline.

Future trials targeting improvements in physical capability should include middle-aged as well as older adults and use measurements of cardio-renal biomarkers as intermediate outcomes.

Low vitamin D levels associated with increased mortality

From a recent study published in Mayo Clinic Proceedings:

Objective

To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and all-cause and cause-specific mortality.

Patients and Methods

We identified all serum 25(OH)D measurements in adults residing in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, through the Rochester Epidemiology Project. All-cause mortality was the primary outcome. Patients were followed up until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Multivariate analyses were adjusted for age, sex, race/ethnicity, month of measurement, and Charlson comorbidity index score.

Results

A total of 11,022 individuals had a 25(OH)D measurement between January 1, 2005, and December 31, 2011, with a mean ± SD value of 30.0±12.9 ng/mL. Mean age was 54.3±17.2 years, and most were female (77.1%) and white (87.6%). There were 723 deaths after a median follow-up of 4.8 years (interquartile range, 3.4-6.2 years). Unadjusted all-cause mortality hazard ratios (HRs) and 95% CIs for 25(OH)D values of less than 12, 12 to 19, and more than 50 ng/mL were 2.6 (95% CI, 2.0-3.2), 1.3 (95% CI, 1.0-1.6), and 1.0 (95% CI, 0.72-1.5), respectively, compared with the reference value of 20 to 50 ng/mL. In a multivariate model, the interaction between the effect of 25(OH)D and race/ethnicity on mortality was significant (P<.001). In white patients, adjusted HRs for 25(OH)D values of less than 12, 12 to 19, 20 to 50, and greater than 50 ng/mL were 2.5 (95% CI, 2.2-2.9), 1.4 (95% CI, 1.2-1.6), 1.0 (referent), and 1.0 (95% CI, 0.81-1.3), respectively. In patients of other race/ethnicity, adjusted HRs were 1.9 (95% CI, 1.5-2.3), 1.7 (95% CI, 1.1-2.6), 1.5 (95% CI, 1.0-2.0), and 2.1 (95% CI, 0.77-5.5).

Conclusion

White patients with 25(OH)D values of less than 20 ng/mL had greater all-cause mortality than those with values of 20 to 50 ng/mL, and white patients had greater mortality associated with low 25(OH)D values than patients of other race/ethnicity. Values of 25(OH)D greater than 50 ng/mL were not associated with all-cause mortality.

Some medical axioms

From Joseph Alpert.

Longer sleep duration is associated with lower CRP levels

---in this study.

Short telomere syndromes

From a recent review:

Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.

Scurvy

Don’t miss it on the wards. The presentation may be atypical.

Nut consumption and health

From a systematic review and meta-analysis:

Background

Although nut consumption has been associated with a reduced risk of cardiovascular disease and all-cause mortality, data on less common causes of death has not been systematically assessed. Previous reviews missed several studies and additional studies have since been published. We therefore conducted a systematic review and meta-analysis of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality.

Methods

PubMed and Embase were searched for prospective studies of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality in adult populations published up to July 19, 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The burden of mortality attributable to low nut consumption was calculated for selected regions.

Results

Twenty studies (29 publications) were included in the meta-analysis. The summary RRs per 28 grams/day increase in nut intake was for coronary heart disease, 0.71 (95% CI: 0.63–0.80, I2 = 47%, n = 11), stroke, 0.93 (95% CI: 0.83–1.05, I2 = 14%, n = 11), cardiovascular disease, 0.79 (95% CI: 0.70–0.88, I2 = 60%, n = 12), total cancer, 0.85 (95% CI: 0.76–0.94, I2 = 42%, n = 8), all-cause mortality, 0.78 (95% CI: 0.72–0.84, I2 = 66%, n = 15), and for mortality from respiratory disease, 0.48 (95% CI: 0.26–0.89, I2 = 61%, n = 3), diabetes, 0.61 (95% CI: 0.43–0.88, I2 = 0%, n = 4), neurodegenerative disease, 0.65 (95% CI: 0.40–1.08, I2 = 5.9%, n = 3), infectious disease, 0.25 (95% CI: 0.07–0.85, I2 = 54%, n = 2), and kidney disease, 0.27 (95% CI: 0.04–1.91, I2 = 61%, n = 2). The results were similar for tree nuts and peanuts. If the associations are causal, an estimated 4.4 million premature deaths in the America, Europe, Southeast Asia, and Western Pacific would be attributable to a nut intake below 20 grams per day in 2013.

Conclusions

Higher nut intake is associated with reduced risk of cardiovascular disease, total cancer and all-cause mortality, and mortality from respiratory disease, diabetes, and infections.

Mind what you eat and lose weight

Benefits of mindful eating.

Possible health benefits of dietary magnesium

Report here.

Physician burnout: a public health crisis

An article looks at how it affects hospitalists.

Burn out drivers for hospitalists: being employees; being robbed of their autonomy as clinicians (after all they just want to be doctors); being given another job (ward secretary, aka CPOE) without additional compensation. One could go on and on.

Less is more: calories that is

Here is a recent review on the benefits of caloric restriction.

How much do we spend on defensive medicine?

From a survey of hospitalists:

The United States spends substantially more per capita for healthcare than any other nation. Defensive medicine is 1 source of such spending, but its extent is unclear. Using a national survey of approximately 1500 US hospitalists, we report the estimates the US hospitalists provided of the percent of resources spent on defensive medicine and correlates of their estimates. We also ascertained how many reported being sued. Sixty-eight percent of eligible recipients responded. Overall, respondents estimated that 37.5% of healthcare costs are due to defensive medicine. Just over 25% of our respondents, including 55% of those in practice for 20 years or more, reported being sued for medical malpractice. Veterans Affairs (VA) hospital affiliation, more years practicing as a physician, being male, and being a non-Hispanic white individual were all independently associated with decreased estimates of resources spent for defensive medicine.

Why are docs the only ones who can’t use jargon?

Via Kevin MD.

What’s wrong with leaders in health care?

Dr. Suneel Dhand says it’s the fact that they’re non-physicians.

That’s partially true. There are docs in health care leadership but their problem is a shift away from the attitude of a clinician: a passion for doing your best for one patient at a time.

Locums versus non-locums in terms of outcomes

It’s quite the thing nowadays to look at large administrative databases and compare outcomes in various categories of physicians (male versus female, FMG versus domestic, age categories, DO versus MD, and on and on). So it was inevitable that someone would compare locums docs versus non-locums docs. Make whatever you will of this:

Design, Setting, and Participants A random sample of Medicare fee-for-service beneficiaries hospitalized during 2009-2014 was used to compare quality and costs of hospital care delivered by locum tenens and non–locum tenens internal medicine physicians.

Exposures Treatment by locum tenens general internal medicine physicians.

Main Outcomes and Measures The primary outcome was 30-day mortality. Secondary outcomes included inpatient Medicare Part B spending, length of stay, and 30-day readmissions. Differences between locum tenens and non–locum tenens physicians were estimated using multivariable logistic regression models adjusted for beneficiary clinical and demographic characteristics and hospital fixed effects, which enabled comparisons of clinical outcomes between physicians practicing within the same hospital. In prespecified subgroup analyses, outcomes were reevaluated among hospitals with different levels of intensity of locum tenens physician use.

Results Of 1 818 873 Medicare admissions treated by general internists, 38 475 (2.1%) received care from a locum tenens physician; 9.3% (4123/44 520) of general internists were temporarily covered by a locum tenens physician at some point. Differences in patient characteristics, demographics, comorbidities, and reason for admission between locum tenens and non–locum tenens physicians were not clinically relevant. Treatment by locum tenens physicians, compared with treatment by non–locum tenens physicians (n = 44 520 physicians), was not associated with a significant difference in 30-day mortality (8.83% vs 8.70%; adjusted difference, 0.14%; 95% CI, −0.18% to 0.45%). Patients treated by locum tenens physicians had significantly higher Part B spending ($1836 vs $1712; adjusted difference, $124; 95% CI, $93 to $154), significantly longer mean length of stay (5.64 days vs 5.21 days; adjusted difference, 0.43 days; 95% CI, 0.34 to 0.52), and significantly lower 30-day readmissions (22.80% vs 23.83%; adjusted difference, −1.00%; 95% CI −1.57% to −0.54%).

Conclusions and Relevance Among hospitalized Medicare beneficiaries treated by a general internist, there were no significant differences in overall 30-day mortality rates among patients treated by locum tenens compared with non–locum tenens physicians. Additional research may help determine hospital-level factors associated with the quality and costs of care related to locum tenens physicians.

That first sentence is a little misleading. Hospital reimbursement for ordinary Medicare patients is not fee for service and hasn’t been since the Prospective Payment System was implemented in 1984.

A few more observations:

The physicians in both categories were, without a doubt, hospitalists.

Although there was no significant difference in mortality the locums docs had longer LOS. The part B spending referred to above would be their rounding and procedure fees, which may mean locums docs tended to code higher for their visits.

Inflammatory markers in obese adolescents

Interesting read.

Clinical status before and outcomes after admission to hospice

From a report from last year:

Background

Prior work has shown that symptoms leading to restrictions in daily activities are common at the end of life. Hospice is a Medicare benefit designed to alleviate distressing symptoms in the last 6 months of life. The effect of hospice on the burden of such symptoms is uncertain.

Methods

From an ongoing cohort study of 754 community-dwelling older persons, aged greater than or equal to 70 years, we evaluated 241 participants who were admitted to hospice from March 1998 to December 2013. A set of 15 physical and psychological symptoms leading to restricted activity (ie, cut down on usual activities or spend at least half the day in bed) were ascertained during monthly telephone interviews in the year before and 3 months after hospice admission.

Results

The prevalence and mean number of restricting symptoms increased progressively until about 2 months before hospice admission, before increasing precipitously to a peak around the time of hospice admission. After the start of hospice, both the prevalence and the mean number of restricting symptoms dropped markedly. For several symptoms deemed most amenable to hospice treatment, including depression and anxiety, the prevalence dropped to levels comparable to or lower than those observed 12 months before the start of hospice. The trends observed in symptom prevalence and mean number of symptoms before and after hospice did not differ appreciably according to hospice admission diagnosis or sex. The median duration of hospice (before death) was only 15 days.

Conclusion

The burden of restricting symptoms increases progressively several months before the start of hospice, peaks around the time of hospice admission, and decreases substantially after the start of hospice. These results, coupled with the short duration of hospice, suggest that earlier referral to hospice may help to alleviate the burden of distressing symptoms at the end of life.

Concierge medicine: it’s totally a thing now

From the American Journal of Medicine.

What is bullying in medicine?

On the playground bullying was picking on someone just because they were weaker or odd in some way. The word has taken on a different meaning in the hospital.

Multiple clinical manifestations of IgG4 related disease (IgG4-RD)

Here are some key issues addressed in a recent review.

What are some of the IgG4 related diseases?

These may coexist in the same patient:

Autoimmune pancreatitis type 1

Mikulicz disease (salivary gland infiltration)

Constrictive pericarditis

Coronary artery aneurysm

Inflammatory abdominal aortic aneurysm (and the related condition retroperitoneal fibrosis)

Sclerosing mediastinitis

Riedel's thyroiditis (and other forms of thyroid involvement)

Sclerosing mastitis

Pulmonary mass or interstitial disease

Hypophysitis

Prostatitis

Lymphadenopathy (Castleman like and other forms)

Tubulointerstitial nephritis

Sclerosing cholangitis (which differs in some features from primary sclerosing cholangitis)

How is IgG4-RD diagnosed?

This has been in a state of some controversy and flux. From the article:

According to an international symposium held in 2011, the diagnosis of IgG4-RD requires both an appropriate histological appearance and increased numbers of IgG4-positive plasma cells (or an elevated IgG4:IgG ratio) in tissue...

In 2011, an “All Japan IgG4 Team,” with the aim to draft comprehensive diagnostic criteria for IgG4-RD 51 ( Table 3 ), proposed three major items 51 69 (1) single or multiple organs involved with diffuse or localized swelling, masses, nodules, and/or hypertrophic lesions; (2) elevated serum IgG4 levels (greater than or equal to 135 mg/dL); and (3) histopathologic features that include marked lymphocytic and plasma cell infiltration and fibrosis, with IgG4-positive plasma cell infiltration (IgG4/IgG-positive cell ratio of greater than or equal to 40% and IgG4-positive plasma cells exceeding 10/HPF). Based on these criteria, patients can be classified into the categories of definite, probable, or possible IgG4-RD.

How do autoimmune pancreatitis (AP) types 1 and 2 differ?

Age: older onset (6^th decade) typical of type 1

Gender: male predominance in type 1, not 2

Relationship to IgG4: present in type 1, not clearly present in 2

Histology: lymphoplasmacytic sclerosing pancreatitis in type 1, idiopathic duct centric pancreatitis in 2

Abdominal pain: common in type 2, not in 1

Other organ involvement common in 1, not 2

Steroid responsiveness characterizes both types but type 1 is more prone to relapse.