Should Older Patients with Subclinical Hypothyroidism be Treated with Thyroid Replacement?

With increasing age, many patients develop subclinical hypothyroidism. Subclinical hypothyroidism is defined by the presence of elevated thyroid stimulating hormone (TSH) but normal free T4 levels. Some patients with subclinical hypothyroidism also have symptoms that are not uncommon with increasing age such as constipation, tiredness, mental slowness, and fatigue.

Prior studies have found no association between treating patients with subclinical hypothyroidism with thyroid replacement therapy and resolution of symptoms. However, very old individuals (older than 80 years) are often not included in the studies.

To examine if treatment of subclinical hypothyroidism with thyroid replacement therapy results in resolution of such symptoms, Moojiraat et al. combined data from two randomized controlled trials. Combining data from two trials results in increased number of patients above 80 (and hence power of the study to detect a difference).

Contrary to expectations, but consistent with previous findings, thyroid replacement therapy does not result in resolution of symptoms in patients with subclinical hypothyroidism. Instead, there may be some increase in adverse events.

Prediction of COPD Exacerbations – ACCEPT Tool

Preventing exacerbations in patients with COPD is a major goal. If we can identify patients who are at higher risk of exacerbations, we may be able to tailor more aggressive therapy to such patients. This will result in better utilization of resources, improved risk/benefit ratio, and will not expose low-risk patients to the adverse effects of aggressive therapies. Thus, predicting exacerbation risk in individual patients can guide these clinical decisions. Unfortunately, there are no externally validated and implementable tools to predict COPD exacerbation.

That is until now: Adibi and colleagues have uploaded their manuscript to a preprint server (bioRxiv) which used data from three randomized trials to develop ACCEPT, a clinical prediction tool based on routinely available predictors for COPD exacerbations. Authors externally validated ACCEPT in a large, multinational prospective cohort. ACCEPT appears to be the first COPD exacerbation prediction tool that jointly estimates the individualized rate and severity of exacerbations. The tool is designed to be easily applicable in clinical practice and is accessible as a web application.

Issues with Current Physician Burnout Research

The relationship of physician burnout with patient outcomes has been often reported but the studies have been of poor quality and/or report the outcomes as perceived by physicians. Obviously, using physician’s perception of burnout and physician’s perception of patient outcomes is circular in nature; a burnout physician may be likely to think that the patient care provided by her is of lower quality.

A systemic review, in Annals of Internal Medicine highlights the similar issue. Moreover, it also shows that where a relationship is shown, the effect sizes tend to be larger suggesting that publication bias may be contributing to preponderance of studies showing an effect (because studies showing no effect are not getting published.

The physician burnout research (and researchers) should start using rigorous scientific methods to define outcomes, predictors, associations, and evaluation of interventions. Otherwise, such an important topic will get a poor reputation due to low-quality research.

National Academy of Medicine Talks about Physician Burnout

In response to concerning rates of depression, stress, and burnout among US medical students and clinicians, the National Academy of Medicine (formerly Institute of Medicine) launched the Action Collaborative on Clinician Well-Being and Resilience in 2017.

Incorporating input from experts in human factors and systems engineering and health informatics, as well as medical, nursing, pharmacy, and dentistry experts and educators, the committee took a systems approach to clinician burnout.

The committee’s systems model for professional well-being and clinician burnout has 3 levels: frontline care delivery, health care organization, and external environment, which together influence the work system factors that contribute to clinician burnout and professional well-being. The work system factors often extend across more than 1 system level (care delivery, health care organization, and external environment), and improvement can occur at every level to relieve workplace stress. The recommendations from the report, organized under 6 overarching goals, reflect the crosscutting nature of the identified factors contributing to clinician burnout and professional well-being.

1. Create positive work environments

2. Create positive learning environments

3. Reduce administrative burden

4. Enable technology solutions

5. Provide support to clinicians and students

6. Invest in research

Angiotensin Receptor Blockers and Suicide Risk

Interesting conclusions in a study reported in the JAMA Network Open:

The use of ARBs may be associated with an increased risk of suicide compared with ACEIs.

Investigators matched 964 cases to 3856 controls. Compared to ACE inhibitors, ARBs were associated with 63% higher risk of death by suicide. The results remained significant (60% increase) when individuals with history of self-harm were excluded.

Proliferation of Risk Factors for Physician Burnout

Several authors have promoted various risk factors for physician burnout. Below are some that I noticed in my email:

Moral Injury:

Kopacz MS, Ames D, Koenig HG. It's time to talk about physician burnout and moral injury. Lancet Psychiatry. 2019 Nov;6(11):e28. doi:10.1016/S2215-0366(19)30385-2. PubMed PMID: 31631880.

Low or lack of Mindfulness:

Lebares CC et al. Key factors for implementing mindfulness-based burnout interventions in surgery. The American Journal of Surgery (in Press)

Lack of Resilience and Grit

Shakir HJ, Cappuzzo JM, Shallwani H, Kwasnicki A, Bullis C, Wang J, Hess RM,Levy EI. Relationship of Grit and Resilience to Burnout Among US NeurosurgeryResidents. World Neurosurg. 2019 Oct 16. pii: S1878- 750(19)32658-0. doi:10.1016/j.wneu.2019.10.043. [Epub ahead of print]  PubMed PMID: 31629138.

Attacks on the Calling of Medicine

Stewart MT, Serwint JR. Burning without burning out: A call to protect thecalling of medicine. Curr Probl Pediatr Adolesc Health Care. 2019 Oct 17:100655. doi: 10.1016/j.cppeds.2019.100655. [Epub ahead of print] PubMed PMID: 31631025

Above are some of the examples of risk factors cited in literature and the list continues to grow with each passing day. There are folks who have developed ‘Burnout Prevention Programs’ around these risk factors. Some even market these programs and make money.

My concern stems from the fact that while there may be strong conceptual underpinnings for at least some of these risk factors, rigorous studies examining the relationship are missing. The current state of evidence is so poor that a clinician will not take seriously risk factors with such limited evidence when managing a patient. Then, why, physicians doing this to themselves.

In particular, the worrisome part is the so-called prevention programs. Where is the evidence to support that such interventions work? If we don’t accept evidence for our patients without randomized clinical trials or at least strong observational studies, why we accept such intervention programs without evidence of efficacy?

Waste in US Healthcare System

US healthcare system is quite unique; it is the costliest system in the world but the outcomes are poor. In other words, the value of healthcare (outcomes/cost) is low and a significant amount expense goes in waste. There have been efforts to reduce waste in the healthcare system but it is unclear how effective such efforts have been.

In one estimate, the overall annual cost of waste in the healthcare is between $760 to $935 billion or 25% of the total healthcare spending. Authors also tried to estimate the amount of waste in different domains. Of interest is that fact that administrative complexity and pricing failure are the largest ticket items but there are only meager attempts to address these.

Below are the numbers:

Domain	Waste (in billions)
Failure of Care Delivery	$102.4 to $165.7
Failure of Care Coordination	$27.2 to $78.2
Low-value Care	$75.7 to $101.2
Pricing Failure	$230.7 to $240.5
Fraud and Abuse	$58.5 to $83.9
Administrative Complexity	$265.6

Selepressin: Not so useful in Septic Shock

Septic shock is an advanced stage of body’s response to an infection and manifests as marked decrease in blood pressure with resulting decrease blood flow (and hence nutrients and oxygen) to the tissues. The decreased blood pressure is due to vasodilatation and increased capillary permeability (leaky capillaries).

The treatment of septic shock includes antibiotics to treat the infection, intravenous fluids to replenish fluid that has seeped out into the tissues from leaky capillaries, and vasopressors (such as norepinephrine) to counter vasodilation. Not uncommonly, norepinephrine is not sufficient to raise blood pressure and increase blood flow to the tissues. Vasopressin, another vasopressor, is sometimes used in addition to norepinephrine to support blood pressure. However, vasopressin has other adverse effects. These adverse effects are due to the fact that vasopressin stimulates three types of vasopressin receptors (V1a, V1b, and V2). Stimulation of V1a has vasopressor effect while stimulation of V1b and V2 results in increased coagulation activity, nitric oxide release, corticosteroid secretion, and excessive water retention.

Selepressin is a selective V1a receptor agonist and has only vasopressor effect. One would assume that selective stimulation of V1a receptors with selepressin will result in beneficial outcome. However, in a clinical trial (N=868), selepressin was not found to be effective in reducing ventilator-free days, norepinephrine-free days, mortality, lower ICU days, or lower need for kidney replacement therapy.

High-Flow Nasal Cannula vs. Noninvasive Ventilation

In patients who are being mechanically ventilated and are at high risk of extubation failure, this randomized controlled trial (N=641) found non-invasive ventilation with high-flow oxygen superior to high-flow nasal cannula alone. Here is the study.