Primecuts – This Week In The Journals

July 25, 2016

poolBy Vishal Shah, MD

Peer Reviewed

A lone 18-year-old gunman opened fire on the public in the vicinity of the Olympia Shopping mall in Munich, Germany this past Friday July 22nd [1]. He carried a 9mm handgun and roughly 300 rounds of ammunition. Nine victims lost their lives and 35 were wounded [2]. The shooter died of a self-inflicted gunshot wound.

Germany has some of the strictest firearm laws in the world [3]. Those younger than 25 who attempt to buy a gun must have a psychiatric evaluation. Fully automatic weapons are prohibited while semi-automatic firearms are banned unless used for hunting or competitive sports. Authorities believe he obtained the gun illegally from the dark-net, a back-alley encrypted network with restricted access where users may obtain contraband such as drugs and firearms [4]. The serial number of the gun that was used had been scratched off; he did not have a permit. While gun laws did not stop the attacker from carrying out his plans, they may have prevented him from getting access to deadlier weapons.

In related news, an observational study on the effectiveness of gun law reforms was in this week’s JAMA. 

Association between Gun Law Reforms and Intentional Firearm Deaths in Australia, 1979-2013

On April 28th, 1996, a man used 2 semiautomatic rifles to kill 35 people and wound 19 others in the Port Arthur massacre in Australia. After this incident, Australia’s state and federal governments responded by passing uniform gun law reform. This included a ban on semiautomatic rifles and pump-action shotguns and rifles, and also initiated a mandatory buyback program of prohibited firearms.

In this week’s issue of JAMA, there was an observational study using Australian government statistics on deaths caused by firearms from 1979-2013 [5]. In the 18 years prior to the ban, there were 13 mass shootings (defined as 5 or more people killed by gunshot) with a mean annual rate of total firearm deaths of 3.6 (95% CI 3.3-3.9) per 100,000. In the 20 years following the ban, no mass shootings have occurred, with a mean annual rate of total firearm deaths being 1.2 (95% CI 1.0-1.4) per 100,000. The annual rate of total homicide was slightly declining from 1979-1996, and after gun law reform, the decline accelerated.

Limitations of the study include its observational nature, which limit the ability to assign causality. Australia is the first known country to enact wide reaching gun reform. Further policy changes and studies will be needed to provide further evidence of the effects of gun reform. A potential first step would be reversing the “Dickey” Amendment, a rider from the 1996 Omnibus effectively limiting the CDC’s ability to fund federal research on gun control/violence [6].

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit

Renal Replacement Therapy (RRT) is often needed in critically ill patients, however, in non-emergent cases, the ideal time to start RRT remains unclear. A trial published in this week’s NEJM aimed to answer this question by randomizing 620 Intensive Care Unit (ICU) patients with acute kidney injury (AKI) to receive RRT using an early versus delayed strategy [7].

Patients were enrolled if they had Kidney Disease: Improving Global Outcomes (KDIGO) score of 3, and required either mechanical ventilation, or catecholamine infusion. Patients were excluded if they had a potentially life-threatening complication directly related to renal failure.

These patients were then randomized to either receive RRT early in hospital course, versus a delayed strategy, wherein RRT was initiated if patients met pre-specified criteria (pH <7.15, Potassium >6, pulmonary edema leading to hypoxia, oliguria persistent for >72 hours, or blood urea nitrogen (BUN) > 112). Of the 620 patients, 80% had sepsis and 63% had been exposed to a nephrotoxic agent. The form of RRT varied, with 55% of patients receiving intermittent RRT and 45% receiving continuous RRT.

The primary outcome was mortality at 60 days. The early RRT group had a mortality of 48.5% [95% CI 42.6-53.8] and the delayed RRT group had a 60 day mortality of 49.7% [95% CI 43.8-55.0], p 0.79]. Limitations include generalizability given the different forms RRT used and study location was only in France. Adverse events included increased percentage of patients undergoing RRT in the early strategy group (98% versus 51%) and increased catheter-related infection rate (10% versus 5%).

The ideal time to start RRT remains unclear. There is no evidence that starting RRT early improves outcomes, but it was associated with increased risk of infection.

Nonrandomized Intervention Study of Naloxone Co-prescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain.

As both opioid prescription and opioid-related overdoses increase, there is growing anxiety about managing these medicines safely in the outpatient setting. In this week’s Annals of Internal Medicine, a study analyzed the benefits of naloxone co-prescription for patients taking chronic opioids [8,9].

This was a nonrandomized intervention study at safety-net primary care clinics, which are a patchwork of individuals, groups, and hospitals that provide primary care to the uninsured, underserved, and other vulnerable populations. The study analyzed 1985 adults receiving long-term opioid therapy for pain. The intervention was training clinicians on prescribing naloxone.

At baseline, patients took an average of 53mg morphine equivalents/day (MME), with 10% of patients taking >400 MME/day. Of the 1985 patients, 38.2% were prescribed naloxone. There was inter-clinic variation in rates of naloxone prescription. Physicians were more likely to prescribe naloxone to patients with a higher risk of overdose, such as those patients on higher doses of opioids, and those with prior ED visits for opioid-related issues. This prescribing pattern reflects the CDC guidelines that were released earlier this year, which advised practitioners to consider offering naloxone to the patients with highest risk of overdose [10].

After 1 year, patients who were prescribed Naloxone had 63% fewer opioid-related ED visits compared with patients who did not have naloxone (Incidence rate ratio (IRR) 0.37 [CI 0.22 – 0.64 p<0.001]). There was no net change of prescription opioid dose by the end of the study (IRR 1.03 [CI 0.91 – 1.27, p 0.61]). No information on actual naloxone usage was collected.

Though there was no clear mortality benefit, a reduction in ED visits is beneficial to both the individual patient and the healthcare system. Therefore naloxone should be considered as an adjunctive therapy, especially for those patients at highest risk of overdosing. However, it is unclear whether the decrease in ED visits was due to naloxone use or from increased awareness of overdose among patients.

State of TeleHealth

Telehealth is the provision of healthcare remotely by means of a variety of telecommunication tools. A review article published in this weeks NEJM gives an overview of the history, current use, limitations, and future directions of telehealth [11].

The early uses of telehealth were to provide care to people who were unable to see a physician in person, such as patients in the military or in rural areas, as well as for acute conditions like cerebrovascular accidents (CVA}. In the past, CVAs were treated in the hospital by a local physician. With the increased use of telemedicine, stroke specialists can provide care remotely, and now the majority of patients with CVA receive specialized care via telemedicine.

Telemedicine is expanding into treatment of chronic conditions as well. Many organizations are beginning to offer low-cost virtual appointments that allow for greater convenience at a lower cost. In fact, Kaiser Permanente predicts that in 2016, it will have more virtual visits than in-person visits.

Among current limitations of telehealth is reimbursement. Twenty-nine states now have telehealth parity laws requiring private insurers to cover telehealth services. If more insurers are to increase reimbursements, more studies will need to perform cost-benefit analysis of particular telehealth programs. Also, many visits are conducted by a physician who has never met with the patient, which can lead to fragmented health care. Additionally, limitations to telehealth include the variability of physician licensing across state lines, the differential access to telecommunications, and the digital divide (which is particularly prominent among patients older than the age of 65).

Despite these limitations, the future of telehealth is promising. The cost of telecommunication is dropping and investments into telehealth are increasing.  In the short term, most of the advances with telehealth will be linked to smartphones. As the number of sophisticated sensors and portable imaging and telecommunications arise, telehealth will expand its reach, enabling more people to receive care. 

Mini cuts:

A 5-year study on early anti-retroviral therapy in patients with HIV-1 was released last week in NEJM [12]. Results suggest that starting ART therapy at the time of diagnosis significantly lowered transmission rates to uninfected partners.

In a study released in May this year the Journal Blood, investigators demonstrated that human neutrophil peptides (HNPs) released from activated neutrophils inhibit the cleavage of von Willebrand factor by ADAMTS13 [13]. This may shed light into the link between inflammation/infection and the onset of microvascular thrombosis in acquired thrombotic thrombocytopenic purpura.

Researchers released a large meta-analysis in JAMA this week comparing clinical outcomes and adverse events associated with anti-diabetic medications in patients with Type II Diabetes [14]. This meta-analysis provides further evidence to continue current standard of care using metformin as a first line agent and utilizing a 2nd agent depending on individual patient characteristics, as no other combination of medications showed significant improvement over one another.

Dr. Vishal Shah is a internal medicine resident at NYU Langone Medical Center

Peer reviewed by David Kudlowitz, MD, chief resident, internal medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons



  1. Callimachi R, Eddy M, Jacobs A. Gunman in Munich Kills 9. New York Times. July 22 2016.
  2. Eddy M. Munich gunman portrayed as having planned attack for a year. New York Times. July 24 2016.
  3. BBC. Munich attack: Calls in Germany for tighter gun laws. July 24, 2016.
  4. Noack R. Germany has some of the world’s strictest gun laws, but illegal weapons remain a threat. The Washington Post. July 23 2016.
  5. Chapman S, Alpers P, Jones M. Association Between Gun Law Reforms and Intentional Firearm Deaths in Australia, 1979-2013. JAMA. 2016;316(3):291-299. doi:10.1001/jama.2016.8752.
  6. Jamieson, C. Gun violence research: History of the federal funding freeze. American Psychological Association. February 2013.
  7. Gaudry S, Hajage D, Schortgen F et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med 2016; 375:122-133. July 14, 2016DOI: 10.1056/NEJMoa1603017
  8. Coffin PO, Behar E, Rowe C et al. Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain. Ann Intern Med. 2016 Jun 28. doi: 10.7326/M15-2771
  9. CDC. Prescription Opioid Overdose Data. CDC. www.cdc.gom/drugoverdose/data/overdose.html 
  10. Dowell, D. Haergerich T. Chou R. CDC Guidelines for Prescribing Opioids for Chronic Pain – United States, 2016. Centers for Disease Control. March 18, 2016.
  11. Dorsey ER and Topol EJ. State of Telehealth. N Engl J Med 2016; 375:154-161July 14, 2016DOI: 10.1056/NEJMra1601705
  12. Cohen MS, Chen YQ, McCauley M et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. 2016. Epub ahead of print. DOI: 10.1056/NEJMoa1600693
  13. Pillai VG, Bao J, Zander C et al. Human neutrophil peptides inhibit cleavage of von Willebran factor by ADAMTS13: a potential link of inflammation to TTP. Blood. 2016; 128:110-119. doi: 10.1182/blood-2015-12-688747
  14. Palmar SC, Mavridis D, Nicolucci A et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes. JAMA. 2016;316(3):313-324. doi:10.1001/jama.2016.9400.