Bisher AKIL, MD

Archive for November, 2019|Monthly archive page

Will This Make Me an Addict?

In General Health, Uncategorized on November 22, 2019 at 4:24 pm

The risk of addiction after a short course of opioids for acute pain is poorly understood. To quantify the risk of ongoing opioid use after a single prescription in the emergency department (ED), researchers prospectively enrolled adult opioid-naive patients with new-onset acute pain who were prescribed an opioid and discharged from the ED. Follow-up was performed at 6 months via telephone call, chart review, and review of a statewide prescription database. Among 484 patients enrolled at two EDs, average age was 46 years and the median pain duration was 2 days. Most patients (88%) were low risk for opioid misuse based on the Opioid Risk Tool. Oxycodone-acetaminophen was the most common opioid prescription (77%). Overall, 102 patients (21%) filled at least one additional opioid prescription within 6 months (the primary outcome). “Persistent opioid use,” defined as at least six prescriptions during the 6-month follow up, occurred in five patients (1%). Of patients with persistent opioid use, prescription frequency decreased over the 6-month follow up period.

Citation:  Friedman BW et al. Opioid use during the six months after an emergency department visit for acute pain: A prospective cohort study. Ann Emerg Med 2019 Nov 1; [e-pub]. (


Summary appeared in NEJM- Journal Watch

Comments: This question comes up quite often; patients may even endure pain for fear of  potential addiction; here is a good, but not great, answer; still 1% met the authors’ definition of persistent opioid use. Patients’ awareness and physician watchful attention are needed to make this practice lower- BA

Hold the Popcorn!

In General Health, Kids & teens on November 22, 2019 at 4:07 pm

Although electronic cigarettes (e-cigarettes) were initially marketed as a potential smoking-cessation aid and a safer alternative to smoking, the long-term health effect of e-cigarette use (“vaping”) is unknown. Vaping e-liquids expose the user to several potentially harmful chemicals, including diacetyl, a flavoring compound known to cause bronchiolitis obliterans (inflammatory obstruction of the lung’s tiniest airways, called bronchioles. The bronchioles become damaged and inflamed by chemical particles or respiratory infections) with inhalational exposure (“popcorn worker’s lung”- described from a number of workers in factories making microwave popcorn developed “popcorn lung” after inhaling the flavoring chemical diacetyl, which is also used in e-liquids ). Here is a case reported by Canadian physicians,  of a 17-year-old male youth who presented with intractable cough, progressive dyspnea (difficult or labored breathing)  and malaise after vaping flavored e-liquids and tetrahydrocannabinol(one of at least 113 cannabinoids identified in cannabis. THC is the principal psychoactive constituent of cannabis) intensively.  He required intubation (a procedure by which a tube is inserted through the mouth down into the trachea – the large airway from the mouth to the lungs), invasive mechanical ventilation and venovenous extracorporeal membrane oxygenation (ECMO) for refractory hypercapnia (a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the body’s metabolism and is normally expelled through the lungs). The patient’s condition improved with high dose corticosteroids. He was weaned off ECMO and mechanical ventilation, and discharged home after 47 days in hospital. Several months after hospital discharge, his exercise tolerance remained limited and pulmonary function tests showed persistent, fixed airflow obstruction with gas trapping. The patient’s clinical picture was suggestive of possible bronchiolitis thought to be secondary to inhalation of flavoring agents in the e-liquids, although the exact mechanism of injury and causative agent are unknown. They concluded that this  case of severe acute bronchiolitis, causing near-fatal hypercapnic respiratory failure and chronic airflow obstruction in a previously healthy Canadian youth, may represent vaping-associated bronchiolitis obliterans. This novel pattern of pulmonary disease associated with vaping appears distinct from the type of alveolar injury predominantly reported in the recent outbreak of cases of vaping associated pulmonary illness in the United States, underscoring the need for further research into all potentially toxic components of e-liquids and tighter regulation of e-cigarettes.

Source:  Simon T. Landman, Inderdeep Dhaliwal, Constance A. Mackenzie, Tereza Martinu, Andrew Steele and Karen J. Bosma CMAJ November 20, 2019 cmaj.191402; DOI:

Summary reported in NEJM_ Journal Watch

Comments:  Yet another one!_BA

Descovy vs. Truvada: tit for tat?

In HIV on November 22, 2019 at 3:38 pm

Current antiretroviral therapy (ART) treatment guidelines and practice have resulted in a pronounced shift from use of tenofovir disoproxil fumarate (TDF – Truvada®) to tenofovir alafenamide (TAF – Descovy®), which is associated with less bone and renal toxicity. Recently, concerns have been raised about increased cholesterol and body weight linked to TAF relative to TDF. In this study, investigators examined changes in cholesterol, body weight, body-mass index (BMI), and American College of Cardiology atherosclerotic cardiovascular disease (ASCVD) risk score in ART-experienced persons living with HIV who switched from TDF to TAF at an academic-based HIV clinic. Before the switch, participants had been on an effective TDF-containing regimen, defined as on TDF >1 year with at least two consecutive HIV RNA levels <200 copies/mL and no levels >200 copies/mL in the previous year.

A total of 110 patients (58% African American; 73% male; mean age, 50; median baseline body weight, 185 pounds; median BMI, 28 kg/m2) met study criteria. During the year after the switch, significant increases were observed in average total cholesterol (by 12.5 mg/dL), LDL cholesterol (by 8.2 mg/dL), HDL cholesterol (by 3 mg/dL), weight (by 3 pounds), BMI (by 0.5 kg/m2), and ASCVD risk score (by 0.4 points). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 BMI increase and a 13% increase in ASCVD risk score.

Source: Schafer JJ et al. Changes in body mass index and atherosclerotic disease risk score after switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Open Forum Infect Dis 2019 Oct 4; 6:ofz414. (

Summary appeared in NEJM Journal Watch – 20191120

Comments: This is a retrospective and small study, with caveats – the majority are African American, male, older, high BMI, only one year follow up- yet the results showing a concerning trend and should be verified by larger and more inclusive study- of note, this is from people with HIV infection, and it may or may not apply for those taking Pre-exposure prophylaxis (PreP). BA

Testosterone Therapy and Blood Clots

In General Health on November 20, 2019 at 9:34 pm

Results from a study published in JAMA Internal Medicine on November 11,2019 was designed  assess whether short-term testosterone therapy exposure is associated with increased short-term risk of venous thromboembolism (VTE or blood clots in veins) in men with and without evidence of hypogonadism.

This case-crossover study analyzed data on 39 622 men from January 1, 2011, to December 31, 2017, with 12 months of follow-up. Men with VTE cases who were free of cancer at baseline and had 12 months of continuous enrollment before the VTE event were identified by International Classification of Diseases codes. Men in the case period were matched with themselves in the control period. Case periods of 6 months, 3 months, and 1 month before the VTE events were defined, with equivalent control periods (6 months, 3 months, and 1 month) in the 6 months before the case period. A total of 39 622 men (mean [SD] age, 57.4 [14.2] years) were enrolled in the study, and 3110 men (7.8%) had evidence of hypogonadism. In age-adjusted models, testosterone therapy use in all case periods was associated with a higher risk of VTE in men with (odds ratio [OR], 2.32; 95% CI, 1.97-2.74) and without (OR, 2.02; 95% CI, 1.47-2.77) hypogonadism. Among men without hypogonadism, the point estimate for testosterone therapy and VTE risk in the 3-month case period was higher for men younger than 65 years (OR, 2.99; 95% CI, 1.91-4.68) than for older men (OR, 1.68; 95% CI, 0.90-3.14), although this interaction was not statistically significant (P = .14).Conclusions   Testosterone therapy was associated with an increase in short-term risk for VTE among men with and without hypogonadism, with some evidence that the association was more pronounced among younger men. These findings suggest that caution should be used when prescribing testosterone therapy.



JAMA Intern Med. Published online November 11, 2019. doi:
Comment: this a retrospective study done by reviewing ,medical record; the cohort is a mix bag in causes, ages and no mentioning of treatment doses; these caveats should be considered when looking at this possibly important finding- need better studies- BA

HIV Treatment & Weight Gain

In General Health, HIV on November 14, 2019 at 5:44 pm

Following initiation of antiretroviral therapy (ART), many people with HIV gain weight as part of their “return to health.” However, certain antiretroviral medications, including integrase inhibitors, are associated with greater weight gain than others. Now, a manufacturer-sponsored pooled analysis of eight of the sponsor’s trials sheds light on risk factors for this weight gain.

Among 5680 people enrolled in randomized trials of initial ART between 2003 and 2015, median weight increase by week 96 was 2.0 kg. Risk factors for greater weight gain included lower baseline CD4 cell count, higher baseline HIV RNA, black race, and female sex. Participants taking integrase inhibitors (INSTIs) gained more weight than those receiving nonnucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors. Among INSTIs, weight gain was greater with bictegravir and dolutegravir than with elvitegravir/cobicistat (4.24, 4.07, and 2.72 kg, respectively). Among NNRTIs, weight gain was greater with rilpivirine than with efavirenz (3.01 vs. 1.7 kg). Among nucleoside reverse transcriptase inhibitors, weight gain was greater with tenofovir alafenamide than with abacavir, tenofovir disoproxil fumarate, or zidovudine (4.25, 3.08, 2.07, and 0.39 kg, respectively). Extreme weight gain (≥10% increase) occurred in 13% of participants in the first 48 weeks and had risk factors similar to those for weight gain overall.

Appeared in NEJM Journal Watch- edited

Citation: Sax PE et al. Weight gain following initiation of antiretroviral therapy: Risk factors in randomized comparative clinical trials. Clin Infect Dis 2019 Oct 14; [e-pub]. (


Comments: HIV infection is often associated with weight loss, particularly if left untreated after the initial infection and that has been thought to be through a mechanism that involves TNF-alpha; now with earlier detection and treatment we see less of wasting; however , newer medications have been reported to be associated with undesirable weight gain; treators have remarked on this and discussed it in meetings; this is the first study to look prospectively at this phenomenon.  Specific integrase inhibitors and tenofovir alafenamide were associated with greater increases than other ART drugs. Unfortunately, the two most effective integrase inhibitors are associated with higher weight gain than the less robust one-

Saved by the Watch?

In Heart on November 14, 2019 at 5:29 pm

The Apple Watch has an optical sensor that can detect heart rates, thus introducing the possibility of detecting atrial fibrillation (AF) [Atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. At least 2.7 million Americans are living with AFib] . The industry-sponsored, prospective [forward] , open-label, siteless, pragmatic Apple Heart Study tested an algorithm to identify AF (NCT03335800). The 419,297 adult U.S. participants enrolled via an app, owned Apple Watches and iPhones, and had no prior AF.

During the study, 2161 people were notified of an irregular pulse, of whom 79% were excluded for various reasons, including 1216 who failed to attend a telemedicine visit. The researchers urgently contacted 20 people: 18 with AF and a rate >200 beats/minute, 1 with a pause >6 seconds, and 1 with non-sustained ventricular tachycardia >6 seconds.

For confirmation, electrocardiographic patches were mailed to 658 participants with nonurgent symptoms. Participants began wearing the patches about 13 days after the notification, for about 6 days. Of 450 people who returned the patches, AF was confirmed in 153 (34%); 20% had continuous AF. The yield was higher in older than younger people. Of 293,015 participants who never received a notification and who returned an end-of-study survey, 3070 reported new AF diagnoses.

As appeared in NEJM – Journal Watch – Edited.

Citations: Perez MV et al. Large-scale assessment of a smartwatch to identify atrial fibrillation. N Engl J Med 2019 Nov 14; 381:1909. (

Campion EW and Jarcho JA. Watched by Apple. N Engl J Med 2019 Nov 14; 381:1964. (


Comments: this is a large study and first of its kind; this maybe what we will see with future studies using wearable health monsters; despite its limitations (no follow up information is a big one), this remains a beginning of a potentially useful mix. Not there yet, though – BA

New HIV Strain

In HIV on November 8, 2019 at 4:58 pm

Researchers have found a new strain of HIV in humans. Here is an edited clip from that paper:

<<The origins of the human immunodeficiency virus (HIV) pandemic have been traced to the Democratic Republic of Congo (DRC), where estimates place the emergence of HIV in the 1920s.  Consistent with an early expansion of HIV in this region, strains from DRC exhibit broad genetic diversity and include all of the recognized subtypes, many circulating recombinant forms (CRFs) [recombinant = genetic material produced when segments of DNA from different sources are joined to produce recombinant DNA] , and an abundance of unique recombinant forms (URFs) and unclassifiable sequences. Current HIV nomenclature [choosing of names for things] guidelines specify that complete genome sequences from at least three non-transmission linked cases are required to establish a new subtype or CRF classification for HIV.>>

This paper in JAIDS had done just that. So now we officially have subtype L.

Source: Complete genome sequence of CG-0018a-01 establishes HIV-1 subtype;  LYamaguchi, Julie BS1; McArthur, Carole MD2; Vallari, Ana MS1; Sthreshley, Larry PhD3; Cloherty, Gavin A. PhD1; Berg, Michael G. PhD1; Rodgers, Mary A. PhD1- JAIDS Journal of Acquired Immune Deficiency Syndromes: November 06, 2019 – Volume Publish Ahead of Print – Issue – doi: 10.1097/QAI.0000000000002246

Free Access to JAIDS article

Appeared in NEJM journal watch November 8, 2019

Comments: As important as this discovery might be from scientific view point, it probably has no impact clinically – BA


Physical Activity and Dementia

In Brain on November 6, 2019 at 3:35 pm

Growing evidence demonstrates that lifestyle behaviors modify dementia risk. Investigators from the Harvard Aging Brain Study assessed the effects of physical activity on β-amyloid ( peptide  crucially involved in Alzheimer’s disease as the main component of the amyloid plaques found in the brains of people with Alzheimer’s disease) burden, longitudinal cognitive decline, and neurodegeneration ( the progressive loss of structure or function of neurons, including death of neurons) in cognitively normal older adults.

Baseline physical activity was the daily number of steps counted over 5 to 7 days by a waistband pedometer (~5500 daily steps in these participants); β-amyloid burden was determined via Pittsburgh Compound B positron emission tomography (Positron emission tomography (PET) is a type of nuclear medicine procedure that measures metabolic activity of the cells of body tissues) , and vascular risk was calculated with the Framingham Heart Study cardiovascular disease risk score (estimates risk of heart attack in 10 years) .  Longitudinal neurodegeneration was measured by loss of gray matter ( part of the brain that contains most of the brain’s neuronal cell bodies) and cortical thickness (Cortex is the outer layer of the brain) seen on brain MRI, and a cognitive composite score indicated cognitive change over time.

Cross-sectional analysis of the 182 participants (57% female; mean age, 73), showed that greater physical activity was associated with lower vascular risk but not with β-amyloid burden. After a follow-up of 5 to 6 years, higher physical activity was associated with slower β-amyloid–related cognitive decline and gray-matter volume loss in multivariable analyses. Lower vascular risk was independently associated with slower β-amyloid–related cognitive decline and volume loss. Exploratory whole-brain analyses associated greater physical activity with slower β-amyloid–related cortical thinning in the entorhinal, insular, lateral temporal, and medial parietal regions but not the hippocampus.

Citation: Rabin JS et al. Associations of physical activity and β-amyloid with longitudinal cognition and neurodegeneration in clinically normal older adults. JAMA Neurol 2019 Jul 16; [e-pub]. (

Appeared in NEJM Journal watch

Comments: many studies indicated that physical activity could help with dementia; this is a longitudinal study with biomarkers demonstrating the benefits- impressive-BA

Eat Meat – really?

In General Health on November 6, 2019 at 12:07 am

Current dietary guidelines implicate unprocessed red meat and processed meat in conferring adverse cardiovascular (CV) and cancer outcomes. However, these guidelines all have one or more limitations (conflict of interest for the authors; observational studies and not clinical trials [RCT]; other factors affecting outcome)

In this new guideline, an independent panel (Sponsoring Organization: Nutritional Recommendations (NutriRECS) international consortium) addresses each of these limitations, using findings from five comprehensive meta-analyses:  One meta-analysis included all randomized, controlled trial (RCT) evidence, three others included data from all observational studies with >1000 participants, and one concerned participants’ values and preferences about meat consumption. The panel’s evaluation produced the following summary results:

  1. Meta-analysis of the 12 RCTs showed no significant difference between patients who consumed higher versus lower quantities of red meat during longer than 10 years of follow-up for the outcomes of all-cause mortality, CV-related mortality, CV disease, or cancer-related mortality, including colorectal cancer.
  2. The observational studies showed that, for every 100 people who reduced processed or unprocessed meat intake by 3 servings per week, roughly 1 person avoided death and 1 person avoided a diagnosis of diabetes during 11 years of follow-up.

A panel suggests that adults may continue to consume unprocessed red meat and processed meat without incurring excess health risks.


Johnston BC et al. Unprocessed red meat and processed meat consumption: Dietary guideline recommendations from the Nutritional Recommendations (NutriRECS) Consortium. Ann Intern Med 2019 Oct 1; [e-pub]. (

Appeared in NEJM Journal Watch: October 24,2019

Comments: These recommendations are actually weak and panel stated they are based on “low-certainty evidence”. Until there is better RCTs with less inherent biases(s), take these meats with a grain of salt-BA

Get Measles, Lose Immunity

In Immune System on November 5, 2019 at 11:42 pm

Measles infection appears to deplete a significant proportion of a person’s antibodies, thereby increasing susceptibility to other infections, according to a study in Science.

During a measles outbreak in the Netherlands, researchers measured antibodies against common viruses among 77 un-vaccinated children both before and 2 months after they were infected with measles. After severe cases of measles, patients lost a median of 40% of their preexisting pathogen-specific antibody repertoires. Children with mild cases lost 33%.

Controls who didn’t develop measles retained about 90% of their repertoires. In addition, children who had been vaccinated against measles-mumps-rubella actually saw increases in their antibody diversity.

The authors say that the antibodies begin to rebuild soon after measles infection. In experiments in monkeys, the depletion lasted for at least 5 months, and the authors say some of the loss may be permanent.

The authors conclude: “These findings underscore the crucial need for continued widespread vaccination.”

Source: Science article (free)

Background: NEJM Journal Watch Infectious Diseases coverage of measles infection despite evidence of immunity – Friday 11/1/2-019

Comments: A strong argument for vaccination, in case another one is needed-BA