Primecuts – This Week in the Journals

August 14, 2018

By Elissa Lin, MD

Peer Reviewed

While the summer brings long daylight hours, it also brings dreaded bugs and mosquitos. Beware of a new tick species, the Asian long-horned tick, Haemaphysalis longicornis. It’s the first new species to arrive in the United States in 50 years and it is spreading along the East Coast, including through the suburbs of New York City [1]. Fortunately, public health experts are not alarmed…yet. This tick species from Asia is more of a threat to livestock than to humans. The ticks have also not been found to carry pathogens for Lyme disease, babesiosis, or erlichiosis.

Now on to some highlights in the medical research world…

A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus (NEJM)

The water deprivation test is the current method of choice for distinguishing central diabetes insipidus (DI) from primary polydipsia. This test, however, can be challenging to perform and difficult to interpret [2]. A multicenter, prospective study found that an alternative test using copeptin, the C-terminal segment of the arginine vasopressin (AVP) prohormone, may be a better alternative [3]. A total of 144 patients with hypotonic polyuria were recruited and underwent both water-deprivation and hypertonic saline infusion tests. Infusion of hypertonic saline raises plasma osmolality and stimulates AVP secretion, much like water deprivation. Thus, high levels of copeptin would indicate primary polydipsia, rather than central DI. Patients with nephrogenic diabetes insipidus were excluded from the study, which found the hypertonic saline infusion test had a diagnostic accuracy of 96.5% (95% CI 92.1%-98.6%) compared to 76.6% (95% CI 68.9%-83.2%) for the indirect water-deprivation test. According to the investigators, a limitation of the hypertonic saline test was its adverse effects, namely vertigo, headache, nausea, and malaise. On the other hand, 62% of patients preferred it over water deprivation.

The Bottom Line: In making the critical distinction between primary polydipsia and central diabetes insipidus, measuring copeptin levels with hypertonic saline infusion is shown to have higher diagnostic accuracy compared to the water deprivation test.

Safety and efficacy of the sodium-glucose cotransporter 1 inhibitor mizagliflozin for functional constipation: a randomised, placebo-controlled, double-blind phase 2 trial (The Lancet)

Functional constipation is associated with decreased quality of life [4], but there are few effective medications for it that do not incur significant adverse effects. A randomized, placebo-controlled, double-blind phase 2 trial was performed to assess mizagliflozin [5], which works by increasing luminal glucose and water, leading to softer stools. 258 patients from 32 hospitals in Japan were recruited and treated with 5 mg or 10 mg of mizagliflozin, or with placebo, for 4 weeks. The primary outcome was change from baseline in number of spontaneous bowel movements after one week. The groups taking mizagliflozin had a significantly greater number of spontaneous bowel movements in one week (3.85 [SD 3.96], p<0.0001 for the 5 mg group and 5.85 [SD 6.01], p<0.0001 for the 10 mg group) compared to the placebo group (1.80 [SD 1.80]). At 4 weeks, results continued to support the efficacy of mizagliflozin. The most frequently observed adverse effects were diarrhea and abdominal distension (33% of patients in both dosage groups compared to 20% in the placebo group). A major study limitation is that patients were only taking the medication for 4 weeks, and so longer-term use will need to be assessed.

The Bottom Line: Mizagliflozin at 5 mg and 10 mg may be an effective and safe treatment for functional constipation.

Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study (Chest)

Because of the high mortality rate associated with pulmonary embolism (PE) [6], treatment has generally occurred on an inpatient basis. A few prospective studies have suggested that outpatient treatment of PE is possible for certain patients, but the Low-Risk Pulmonary Embolism (LoPE) study [7] was designed to specifically address the safety and efficacy of outpatient management. In this prospective cohort study, patients diagnosed with low-risk acute PE (a Pulmonary Embolism Severity Index score less than 86) were either observed for 12 or 24 hours in a standard ED bed, or in the hospital under outpatient observation status. About 29% of patients were excluded due to conditions including hypoxia and signs of right heart strain on echocardiogram. Treatment was determined by the emergency physician. The primary outcome was a composite of symptomatic recurrent VTE, major bleeding, or mortality within 90 days of enrollment. Results showed a composite rate of 0.5% (95% CI 0.02%-2.36%), without any deaths. In other words, out of 200 patients, only one had an adverse event (major bleed on day 61 due to a traumatic thigh injury). 91% of patients were highly satisfied with their care.

The Bottom Line: Diagnosis of low-risk acute PE by a PESI score less than 86 may help select patients to be safely treated for PE on an outpatient basis.

Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis (Clinical Infectious Diseases) 

When a patient aspirates, clinicians may be quick to use antibiotics in the setting of fever, especially given the challenge in distinguishing aspiration pneumonia from pneumonitis. A retrospective cohort study was performed to determine the potential benefits and harms of this practice by comparing outcomes among patients with aspiration pneumonitis who received prophylactic antimicrobial therapy versus supportive care alone [8]. Inclusion criteria included those with clinical documentation confirming a macroaspiration event and chest radiograph features of a new infiltrate. Patients who received antimicrobials within 2 days of macroaspiration were labeled as receiving prophylaxis while those outside this window were classified as receiving supportive care. There was no significant difference in 30-day mortality between the two groups (adjusted OR 0.85, 95% CI 0.42-1.74, p value 0.7). In fact, 8% of those receiving antimicrobial prophylaxis required escalation of antimicrobial therapy, versus 1% in the supportive care group (p value .008). The study has several limitations, including its size (200 patients). Additionally, the study was unable to evaluate the impact of antimicrobials on the development of pneumonia.

The Bottom Line:  Compared to supportive care, prophylactic antimicrobial treatment does not offer clinical benefit to patients with acute aspiration pneumonitis following a macroaspiration event.


Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults (NEJM)

Investigators conducted a randomized controlled trial and found that a 4-month regimen of rifampin was not inferior to a 9-month regimen of isoniazid for latent tuberculosis [9] A much shorter treatment could mean greater compliance and help reduce the burden of tuberculosis. 

Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care: A Matched Cohort Study (Annals of Internal Medicine) 

A multicenter study of adults with Type 2 DM found that bariatric surgery was associated with lower overall incidence of microvascular disease including a lower cumulative incidence of diabetic neuropathy at 5 years compared to nonsurgical care (7.2% surgical vs. 21.4% nonsurgical; HR 0.37 CI 0.30-0.47) [10].

Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones: A Randomized Clinical Trial (JAMA)

In a double-blind, placebo-controlled clinical trial, tamsulosin did not significantly increase the passage rate of symptomatic urinary stones <9 mm compared to placebo [11]. Guidelines for treatment of renal colic due to small stones may need to be revised, though there may still be use for tamsulosin in the expulsion of larger stones.

Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides (Annals of the Rheum Diseases)

A trial compared rituximab with azathioprine in maintaining remission among patients with newly diagnosed or relapsing anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides and found rituximab was superior over 60 months [12]. This further supports the use of Rituximab as a long-term treatment of these diseases, along with its steroid-sparing benefits.

Dr. Elissa Lin is a first-year internal medicine resident at NYU Langone Health

 Peer reviewed by Christian Torres, MD, associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons 


  1. McNeil Jr, Donald G. “An Invasive New Tick is Spreading in the U.S.”. NY Times 2018 Aug 6.
  2. De Fost M et al. The water deprivation test and a potential role for the arginine vasopressin precursor copeptin to differentiate diabetes insipidus from primary polydipsia. Endocr Connect 2015 Jun 4;4(2):86-91.
  3. Fenske W et al. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med 2018 Aug 2;379:428-439.
  4. Wald A et al. The burden of constipation on quality of life: results of a multinational survey. AP&T 2007 May 15;26(2):227-236
  5. Fukudo S et al. Safety and efficacy of the sodium-glucose cotransporter 1 inhibitor mizagliflozin for functional constipation: a randomised, placebo-controlled, double-blind phase 2 trial. The Lancet 2018 Sep 1;3(9):603-613.
  6. Belohlavek J. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol 2013 Spring;18(2):129-138.
  7. Bledsoe JR et al. Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study. Chest 2018 Aug;154(2):249-256.
  8. Dragan V et al. Prophylactic antimicrobial therapy for acute aspiration pneumonitis. Clinical Infectious Diseases 2018 Aug 1;67(4):513-518.
  9. Menzies D et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. NEJM 2018 Aug 2;379:440-453.
  10. O’Brien R. Microvascular outcomes in patients with diabetes after bariatric surgery versus usual care: a matched cohort study. Annals of Internal Medicine 2018 Aug 7; [e-pub].
  11. Meltzer AC et al. Effect of tamsulosin on passage of symptomatic ureteral stones: a randomized clinical trial. JAMA 2018 August;178(8):1051-1057.
  12. Terrier B et al. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Annals of the Rheumatic Diseases 2018;77:1150-1156.