High Utilizers and Social Support

There is a common theme within the readmission reduction community that a large number of readmissions are due to limited social network around patients and only if we can provide patients with resources in community, we will be able to decrease these readmissions. Some observations studies have noticed a decrease in readmissions when patients are provided access to social/community resources, however, such studies are limited by risk of bias due to the ‘regression to the mean’ phenomenon.

Regression to mean phenomenon stipulates that if we examine participants once only performing a certain activity (or for an outcome), some of them will perform better while others will perform poorly simply due to some random factors. If we observe these participants longitudinally, we will find that those who performed well will perform poorly while those who performed poorly will perform better than their initial performance. Both groups will try to reach towards their mean (or true value).

Similarly, when we examine high-utilizer patients of health care services during a given period, those patients are likely at their worst and will do better anyway during the follow-up. This has nothing to do with the intervention but rather due to the regression to mean phenomenon. The way to address this problem is either to have several longitudinal measurements of the whole cohort where we can identify regression to the mean or to conduct a randomized clinical trial.

Finkelstein et al., conducted such a trial. They randomly assigned 800 hospitalized patients with medically and socially complex conditions with at least one additional hospitalization in the preceding 6 months, to either usual care (control group) or to the intervention group where social workers and community health workers coordinated and helped patients to access community resources.

To their, and frankly everyone else’s, surprise, they found to benefit of all the efforts of social workers and community health workers in reducing readmissions. The 180-day readmission rate was 62.3% in the intervention group and 61.7% in the control group. The adjusted between-group difference was not significant (0.82 percentage points; 95% confidence interval, −5.97 to 7.61).

More importantly, study highlighted the phenomenon of regression to the mean showing that the patients with high readmission rates resulting in enrollment generally had a decline in their readmission rate irrespective of whether they received intervention or not.

The study has few caveats but still raises very important questions – what should hospitals, healthcare systems, physicians, and other healthcare team members do to reduce readmissions and healthcare resource utilization in a very vulnerable population.

Are Young Women Getting Unnecessary Medical Care?

The annual pelvic examination in otherwise healthy women is considered part of the well-woman visit. Similarly, Pap-smear is performed for cervical cancer screening among sexually active women. Screening for cervical cancer is not recommended for women younger than 21 years, a consensus reached by the US Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and American Cancer Society. The general recommendation is against performing pelvic examinations in asymptomatic, nonpregnant women younger than 21 years. However, young women are still undergoing such exams during their physical examinations.

How big is the problem of these unnecessary exams? Qin et al has recently published their findings using the National Survey of Family Growth. They estimated that between 2011 and 2017, an estimated 2.6 million women aged 15 to 20 years in the United States (22.9%) received a pelvic examination in the past year, and 54.4% of these examinations were potentially unnecessary. Further, an estimated 2.2 million young women (19.2%) received a Pap-smear test in the past year, and 71.9% of these tests were potentially unnecessary.

The Best Time to Take Your Blood Pressure Pills

Majority of blood pressure medicines are one daily and people take their blood pressure medicines often in the morning. There have been some data based on our understanding of the diurnal variations or circadian rhythms that taking medications at bedtime may work better. For example, peak activity of the renin–angiotensin–aldosterone system (RAAS) occurs during sleep. Further, data from some uncontrolled studies have suggested that taking blood pressure medications at evening (or bedtime) may be beneficial. However, a randomized controlled clinical trial (the gold standard for scientific evidence) has been lacking. That is until now!

A recent study published in the European Heart Journal, by Hermida et al, addressed this very same question. Investigators enrolled 19 084 hypertensive patients (10 614 men and 8470 women) and assigned patients to take the entire dose of their blood pressure pills at bedtime or in the morning. Of all the patients, 1752 experienced either a death due to heart attack, heart attack without death, had stent placed in their heart blood vessels, developed new heart failure, or a stroke. Patients who were taking their medications had 45% lower risk of all outcomes combined, 56% lower risk of heart attach death, 34% lower risk of heart attack, 40% lower risk of stents in their heart blood vessels, 42% lower risk of heart failure, and 49% lower risk of stroke.

Note, these are large differences – these patients were taking their blood pressure pills but just taking pills at a different time made a huge difference. The difference is larger than many other pills that are often prescribed by physicians. If you, or your loved one, takes blood pressure pills, consider talking to your doctor if you should take your pills at bed-time.

Tele-Health and Liver Transplant

Liver transplantation is the only treatment that increases survival times of patients with decompensated cirrhosis. Patients who live further away from a transplant center are disadvantaged. Health care delivery via telehealth is an effective way to remotely manage patients with decompensated cirrhosis. Authors investigated the effects of telehealth on the liver transplant evaluation process.

Using regression models, authors evaluated the differential effects of telehealth vs. usual care on placement on the liver transplant waitlist. We also investigated the effects of telehealth on time from referral to initial evaluation by a transplant hepatologist, liver transplantation, and mortality.

Authors found that the use of telehealth was associated with a substantial reduction in time from referral to initial evaluation by a hepatologist and placement on the liver transplant waitlist-especially for patients with low MELD scores, with no changes in time to transplantation or pre-transplant mortality.

Maintaining Competency and Physician Responsibility

Santen et al wrote a viewpoint in JAMA and propose the following 5 considerations to address competency decline with age and with introduction of new technology and/or procedures.

1. Lifelong learning and mechanisms to ensure maintenance of certification.
2. Responsibility to keep training.
3. Choosing practices that involve less exposure to procedures or content for which physicians are no longer expert
4. Self-assessment and reflection.
5. Responsibility of the health care system to ensure competency of physicians and surgeons for performing procedures.

These proposals are common sense or a no-brainer. However, the devil is always in the details. For example, how to assess lifelong learning? What is the evidence behind certain methods of lifelong learning? Is it possible that the physicians who self-reflect and self-assess are the ones who need it the least? If so, how to encourage physicians to self-reflect? One can go on and on but I hope I made the point. But I want to make a larger point. Medical education obsessively teaches evidence-based medicine, however, very few, if any, medical education methods have even a weak evidence to support them (as long as we do not include expert advice into evidence). It will be rare to see any medical education methodology that has been rigorously studied like we study medical interventions. No wonder we have increasing burnout among medical students, residents, and physicians; it is time we face the fact that our prescriptions for teaching medicine lack scientific evidence.

Fragility Index for Randomized Controlled Trials

An interesting question – how ‘fragile’ are the results of a randomized controlled trial (RCT)?

RCTs are gold-standard for determining the efficacy of a treatment. RCTs randomly assigned patients to an intervention arm or to a placebo (or standard of care or active treatment) arm. Because patients are randomly assigned, we expect that all patient characteristics (genetic, environmental etc.) would be balanced in the two groups. RCTs are often published with significant results – small RCTs without significant results are generally either not published or published in low-tier journals and don’t get prominence

Even when we randomly assign patients to a treatment arm or control arm, there is always a possibility that the two arm may be imbalanced by chance on measured or unmeasured variables. Further, it is also possible that just by chance one group may have statistically significant result than the other group without any true benefit (or harm) of the treatment. While we generally use a p-value of less than 0.05 (which says that there is a 1 in 20 probability that the results are observed due to chance only – not the right definition but its simple!), there remains a small chance that results will be not significant.

In comes ‘Fragility Index’, a measure of determining the robustness of results. Fragility index is the minimum number of patients who must be moved from the nonevent group to the event group to turn a significant result nonsignificant. The fragility index is an easy to calculate index that provides an intuitive way to understand the precision of trial results. Knowing the fragility index and comparing it to the number of patients lost to follow-up can help to understand the uncertainty in evidence even when a study has positive results.

Khan et al, examined cardiovascular clinical trials published between 2007-17 in major Cardiology journals. All trials were large with >500 patient enrollment. Among the 123 RCTs the median fragility index was 13.In almost 1/3rd of trials, the number of patients lost to follow-up was more than the fragility index.

In another study Gaudino et al examined the clinical trials used to support evidence in cardiology guidelines and determined the fragility index. They found that more than a quarter of RCTs supporting current guidelines on myocardial revascularization have a fragility index 3 or lower. Further over 40% of trials had a fragility index which was lower than the number of patients lost to follow-up.

Vaso-Occlusive Crisis in Sickle Cell Patients

Hemoglobin S (HbS) is an abnormal form of hemoglobin and is transmitted through genetically from parents to a child. Normal hemoglobin is mostly made up of 4 globin chains; 2 alpha chains and 2 beta chains. The underlying problem is a single mutation in the beta-chain of the hemoglobin where adenine nucleotide is replaced with a thymidine nucleotide resulting in a missense mutation and changing the amino acid glutamate at no. 6 position with valine. This change in amino acids from glutamate to valine results in changes in the 3-dimensional structure of the beta-chain of hemoglobin. These changes include 1) lower affinity for oxygen, 2) ability to join with other hemoglobin molecules and form polymers, 3) increase oxidation of the RBC cell membrane proteins.

Normal hemoglobin gets oxygenated in the lungs and carries oxygen to the tissues. Oxygen is released in the tissues and hemoglobin gets deoxygenated and returns back to the lungs for oxygenation. Normal hemoglobin remains soluble within the RBC throughout this process. On the other hand, deoxygenated HbS starts forming long filamentous through polymerization of hemoglobin molecules. Importantly, the process takes several seconds in fresh red blood cells (RBC) before polymerizations occurs and there is sufficient time for RBCs to return back to the lungs and get oxygenated.

However, some cells continue to get stuck in blood vessels resulting in completion of polymerization and breakdown of RBCs within the vessels (called intravascular hemolysis). This chronic, slow process of premature destruction of RBC in sickle cell patients is the reason for chronic anemia as well as other slowly developing manifestations of sickle cell disease.

In sickle cell vaso-occlusive crisis, large number of blood vessels are blocked resulting in marked pain and morbidity. Typically, the crisis is precipitated by some event, such as dehydration or an infection. The event stimulates the vascular endothelium making them sticky through expression of cell-binding receptors on the surface. These receptors then bind with other receptors on the surface of RBCs, white blood cells, and platelets resulting in blockage of the vessel lumen. The red blood cells with HbS are already primed to binding with other cells through expression of certain proteins as well as exposure of certain lipid products on the surface. Thus, the vaso-occlusive crisis results from the interaction of HbS containing RBC, endothelium, white blood cells, and platelets.

Physician Burnout & Patient Satisfaction/Experience

There have been concerns that physician burnout leads to lower patient satisfaction. In fact, some studies have found that patient satisfaction is lower among physicians with higher levels of burnout. A meta-analysis published in 2018 assimilated data and reached to the same conclusion. However, the quality of data, and studies, is questionable and there is a need for better conducted studies to examine this relationship.

A recently published article, by Howell et al., in the Journal of Patient Experience found no relationship between patient satisfaction and physician burnout domains of exhaustion and disengagement. This is an interesting finding and has strong implications. What it shows is that despite having high levels of burnout, physicians are able to function in a way that their patients don’t see a difference based on their burnout level. The brunt of burnout is faced by physicians and they shield their patients from its effects, likely at high personal cost.

Obviously, there may be other explanations – for example, the tools used to measure physician burnout are not reliably measuring burnout or that the tools to measure patient satisfaction with physicians are inaccurate and have large measurement bias. Both of these two explanations are possible but less plausible.

AI in Health Care–National Academy of Medicine’s Perspective

Here is the full report

Here are some highlights:

1. Promoting population-representative data with accessibility, standardization, and quality is imperative
2. Prioritize ethical, equitable, and inclusive health care AI while addressing explicit and implicit bias
3. Contextualizing the dialogue of transparency and trust requires accepting differential needs.
4. Near-term focus is needed on augmented intelligence vs AI autonomous agents
5. Develop and deploy appropriate training and educational programs to support health care AI.
6. Leverage frameworks and best practices for learning health care systems, human factors, and implementation science to address the challenges in operationalizing health care AI
7. Balance innovation with safety via regulation and legislation to promote trust.

Vasodilatation in Acute Heart Failure

Acute heart failure is a condition when the cardiac output (the amount of blood pumped by heart every minutes) is not sufficient to meet the needs of the body. Cardiac output depends on how much blood is in the heart before it starts contracting (cardiac pre-load), how strongly hear contracts (cardiac contractility), how much resistance heart faces when pumping blood into the arteries (cardiac after-load, or peripheral vasoconstriction), and how many times heart beats in a minutes.

For a failing heart, increasing the force of contraction and decreasing the pressure against which it pumps blood (after-load or vasoconstriction) are important factors. In fact, peripheral vasodilators such as ACE inhibitors or ARB are standards of care for heart failure patients. One may ask, what if we decrease the pressure against which heart pumps blood really low, in other words, if we cause high (intensive) vasodilation with drugs. This particular hypothesis was tested in The GALACTIC Study recently published in JAMA.

Interestingly, authors found no benefit of intensive vasodilatation on composite endpoint of death or rehospitalization. Further, the intensive vasodilation arm had higher risk of adverse effects such as worsening renal function, hypokalemia, dizziness, and hypotension.

The results are important because they suggest that while we focus on cardiac output, blood flow to individual organ (or fraction of cardiac output received by various organs may be as important, if not more important. Intensive vasodilatation likely results in poor perfusion to various organ resulting in increased adverse effects.

Sleepiness after work, Burnout, and Empathy

Tiredness after work, particularly shift work is common. How this relates to burnout and empathy is poorly explored. This study assessed the effects of shift (Day, Night), time of day (AM, PM), and gender (Male, Female) on sleepiness, empathy, and burnout in medical students. Working a 12 h night shift resulted in increased sleepiness as compared to a 12 h day shift. Sleepiness after a night shift resulted in differences in empathy. The sleepier the participant after working the 12 h shift, the lower their emotional empathy score.Similarly, sleepiness was associated with higher levels of burnout and females were affected more than men.

Artificial Intelligence in a Smartwatch for Atrial Fibrillation

An interesting study by Perez et al in NEJM found some very interesting things:

1. A large number of people opted-in to be part of the study (over 400K)
2. In about 4 months, about 0.5% participants were noted to have irregular heart rate – a relatively small percentage than one would expect.
3. Of the people who returned 7-day monitoring after being notified of irregular heart beat, about one-third had atrial fibrillation. This is a significant number of atrial fibrillation in otherwise asymptomatic individuals.

The study highlights several important things, some noted above. However, what it does not tell us if the use of smartwatch to identify atrial fibrillation in otherwise healthy people results in improved health outcomes or not. A future study should be able to evaluate this question. For now, at least we know we can depend on smartwatch to identify atrial fibrillation.

Burnout among Nurses

Dyrbye et al conducted a national survey of the US nurses (response rate 26.2%) and found that 35.3% had burnout symptoms. Interestingly, 30.7% of the respondents also had symptoms of depression. Quite interestingly, authors found that nurses who had higher burnout were more likely to have been absent 1 or more days during the last month and had poor work-performance.

Critique: Authors need to be commended for conducting a national study of nurses. However, this study has the same issue that we find in other burnout literature; person who is burnout is also the one who determines if they have poor performance or not. At least theoretically, one would assume that a person who is burnout will look more negatively towards themselves and their work than a person who is not burned out; we would expect a high correlation between the two. On the other hand, a study in which nurses’ superiors could have been asked to comment on performance would have generated more reliable data, however, such study would have been quite expensive requiring significant external funding.

Burnout in Healthcare–A systems approach

Interesting and thought-provoking analytical piece by Montgomery et al which correctly points out that the responsibility of mitigating burnout lies with the institution and that the practice of putting the responsibility on healthcare workers should be abandoned. Currently, most places try to focus on the healthcare worker – asking them to take better care of themselves, be resilient, cope with stressors on their own, etc. They propose the following:

1. Provider burnout should be added to the current assessment of healthcare quality
2. Burnout should be assessed at the departmental/unit level (and I would add that it should be measured at least annually).
3. Development of health workplaces should be a major goal
4. Key questions concerning research and practice should not be coming from researchers alone.

Personally, I do believe that there are not enough researchers examining the interventions needed to address burnout. There is lack of funding from national funding agencies and from locally from institutions.

Some Recent Physician Burnout Literature

An abstract, presented at the the annual meeting and published in the Journal of American College of Surgeons’ supplement examined relationship between burnout and involvement of surgeons in medical device development/innovation.

As is often found in medical students across the world, New Zealand’s medical students also appear to have high levels of burnout. Farrell et al surveyed one of the two medical school in New Zealand and found that the prevalence of exhaustion was 77% while of disengagement was 68%. Another proof that burnout in medical profession is a worldwide phenomenon.

A study examined burnout among Egyptian ICU physicians and found interesting results. The level of exhaustion was 38.8%, somewhat better than generally found in the West. However, the level of depersonalization was 70.1%. This is really surprising; do Egyptian physicians really feel that much disconnected or disengaged from their patients?

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.