Naloxone administered in the field by EMS personnel safe for reversing opioid overdose

1. Naloxone administered in the field by EMS personnel is safe and effective for reversing opioid overdose

More research needed to determine the optimal dose and route of administration of naloxone

Abstract: http://annals.org/aim/article/doi/10.7326/M17-2224

Editorial: http://annals.org/aim/article/doi/10.7326/M17-2963

URLs go live when the embargo lifts

Naloxone administered in the field by emergency medical services (EMS) personnel, either by nasal spray or injection, is safe and effective for reversing opioid overdose symptoms. However, research is needed to understand the optimal dose and route of administration of naloxone. Nontransport to the hospital after reversal of overdose did not seem to be associated with serious harms. The results of a systematic evidence review are published in Annals of Internal Medicine.

Drug overdose is now the leading cause of injury-related death in the United States and opioid misuse has been deemed a national public health emergency. Opioid overdose is frequently treated with naloxone in the field by EMS personnel, but evidence to inform optimal management of suspected overdose in out-of-hospital settings is limited.

Researchers for the Agency for Healthcare Research and Quality reviewed 13 published studies to determine the effects of route of administration and dosing of naloxone in persons with suspected opioid overdose in an out-of-hospital setting on mortality, reversal of overdose symptoms, and harms, and the need for transport to a health care facility after reversal of overdose. The evidence showed that higher-concentration intranasal naloxone had similar efficacy to that of intramuscular naloxone for reversal of opioid overdose symptoms with no difference in adverse events. However, evidence on the comparative effectiveness of intranasal and intramuscular naloxone formulations recently approved by the FDA are lacking.

Nontransport of patients after successful reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study directly compared the risk associated with transport versus nontransport, and persons who weren't transported were probably those who responded well to naloxone.

These findings highlight the importance of administering naloxone out of the hospital setting and may inform EMS guidelines for naloxone use. It is imperative that naloxone be administered in a timely manner to maximize its benefits and prevent opioid overdose death and that the naloxone given effectively reverses overdose symptoms. Of particular recent concern is whether current methods of administering and dosing naloxone are sufficient to effectively reverse overdose related to highly potent, illicit fentanyl and fentanyl-like products. As such, future investigations should examine how the effectiveness of naloxone by different doses and routes of administration is affected by the opioid involved in the overdose, and whether off-label administration of intranasal naloxone using a lower concentration formulation is as effective as FDA-approved formulations.

Media contacts: For an embargoed PDF, please contact Angela Collom. To interview the lead author, Roger Chou, MD, please contact Tracy Brawley at brawley@ohsu.edu.

Biennial biopsies may be an acceptable alternative to annual biopsies for men undergoing active surveillance for low-risk prostate cancer. The consequences of annual versus biennial biopsies were found to be similar across four separate cohorts of men with a Gleason score (a scale used to measure severity of cancer cells) between 2 and 6 and clinical state T1 or T2 prostate cancer. The findings are published in Annals of Internal Medicine.

Active surveillance is now the preferred approach for managing newly diagnosed, low-risk prostate cancer, but current guidelines lack specific information about how active surveillance should be implemented. Several studies in North America and Europe are investigating the outcomes of active surveillance, but they involve different populations, follow-up durations, inclusion criteria, surveillance protocols, and definitions of progression that lead to treatment referral. Having data from several active surveillance cohorts provides an opportunity to learn more about disease progression on active surveillance.

Researchers from Fred Hutchinson Cancer Research Center compared PSA levels and biopsy Gleason scores for 2,576 men who were enrolled in an active surveillance study at one of four sites: Johns Hopkins University (JHU); Canary Prostate Active Surveillance Study (PASS); University of California, San Francisco (UCSF); and the University of Toronto (UT) between 1995 and 2014. They observed that risks for cancer upgrading did not generalize from one cohort to another even after controlling for differences in eligibility criteria, surveillance protocols, and competing treatments. Despite this challenge, expected delays in detecting upgraded cancer under more versus less intensive biopsy frequency was robust across cohorts. This analysis suggests that biennial rather than annual biopsies may be justified, particularly given the invasiveness and potential morbidity of annual biopsies.

According to the researchers, these findings provide quantitative justification for the American Society of Clinical Oncology guideline, which also recommends less frequent biopsies after confirmatory biopsy within a year of entering active surveillance.

Media contacts: For an embargoed PDF, please contact Angela Collom. For more information or interview requests, please contact Claire Hudson at crhudson@fredhutch.org or 206-667-7365.

3. Women with one or more negative HPV and cytology co-test may safely extend cervical cancer screening intervals
Abstract: http://annals.org/aim/article/doi/10.7326/M17-1609
Editorial: http://annals.org/aim/article/doi/10.7326/M17-2872
URLs go live when the embargo lifts

After one or more negative cervical co-test with human papillomavirus (HPV) and cytology screening, it may be safe for women to extend their cervical cancer screening intervals to every five years or more. The findings of an observational cohort study are published in Annals of Internal Medicine.

HPV causes almost all cases of cervical cancer and its precursors, therefore screening remains very important. Testing for HPV is more sensitive than cytology-based screening for detecting treatable cervical cancer and precancer, including cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS). HPV testing also provides greater protection against invasive cervical cancer than cytology-based screening. As such, current guidelines recommend concurrent high-risk HPV and cytology testing, or co-testing, at 5-year intervals, with cytology every 3 years as an acceptable alternative. However, these guidelines do not consider previous screening history, because data on multiple-round co-testing have been unavailable.

Researchers for the National Institutes of Health/National Cancer Institute reviewed data for 990,013 women in Kaiser Permanente's integrated health care system to investigate how low cervical cancer risk could become by screening with one or more rounds of HPV and cytology co-testing. They found that women with a screening history showing an increasing number of negative co-tests had a steadily decreasing risk for future cancer, CIN3, or AIS, although the first negative co-test had the greatest effect on risk reduction.

The researchers also found that older women (aged 50 or older) who had their third consecutive negative co-test had a five- to six-fold lower risk of cancer or its precursors than women aged 30 to 39 years who had their first negative co-test. These findings suggest that screening intervals might be assigned on the basis of both age and number of previous negative screens.

Media contacts: For an embargoed PDF, please contact Angela Collom. For an interview with the lead author, Philip Castle, PhD, MPH, please contact Deirdre Branley at deirdre.branley@einstein.yu.edu.

4. Allergy specialists groups release guidelines for treating seasonal allergic rhinitis
Abstract: http://annals.org/aim/article/doi/10.7326/M17-2203
URLs go live when the embargo lifts

The Joint Task Force on Practice Parameters (Joint Task Force) has issued three recommendations for drug treatment of seasonal allergies for people 12 years old or older. The recommendations support intranasal corticosteroids over other drug therapies or in combination with another drug. A synopsis of the recommendations is published in Annals of Internal Medicine.

Seasonal allergies affect up to 14 percent of the U.S. adult population. Most patients who consult an allergy and immunology specialist have already tried many over-the-counter monotherapies without success and are seeking more effective treatment. No consensus exists about whether a particular medication should be used for initial treatment or about the benefit of using two or more medications concurrently for initial treatment.

The Joint Task Force developed the following evidence-based guidelines to inform treatment of seasonal allergic rhinitis in patients aged 12 and older:

1. For initial treatment of people 12 years old or older, the Joint Task Force recommends treatment with an intranasal corticosteroid alone, rather than in combination with an oral antihistamine. The Joint Task Force did not find evidence proving a benefit of adding an oral antihistamine to an intranasal corticosteroid and recognized that oral antihistamines, mainly first-generation, may cause sedation and other adverse effects.

2. For initial treatment of people 15 years old or older, the Joint Task Force recommends treatment with an intranasal corticosteroid over a leukotriene receptor antagonist. The Joint Task Force found evidence clearly showing that an intranasal corticosteroid was more effective than a leukotriene receptor antagonist for nasal symptom reduction.

3. For treatment of moderate to severe seasonal allergies in persons 12 years old or older, the clinician may recommend the combination of an intranasal corticosteroid and an intranasal antihistamine for initial treatment, the Joint Task Force advises. The evidence showed that the addition of an intranasal antihistamine to an intranasal corticosteroid in patients with moderate-to-severe seasonal allergic rhinitis provides additional benefit, in contrast to combination therapy with an intranasal corticosteroid and an oral antihistamine.

The Joint Task Force is comprised of volunteers from the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Three patient advocates were invited to participate in the development of the final recommendations.

Media contacts: For an embargoed PDF, please contact Angela Collom. To interview a study author, please contact the aaai media office at media@aaai.org.

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Also in this issue:

Diagnosing Resistance to a PCSK9 Inhibitor
Michael D. Shapiro, DO; Joshua Mles, BA, Hagai Tavoiri, PhD; Sergio Fazio, MD, PhD
Brief Research Report
Abstract: http://annals.org/aim/article/doi/10.7326/M17-2485

The Value-Based Payment Modifier: Program Outcomes and Implications for Disparities
Eric T. Roberts, PhD; Alan M. Zaslavsky, PhD; J. Michael McWilliams, MD, PhD
Original Research
Abstract: http://annals.org/aim/article/doi/10.7326/M17-1740
Editorial: http://annals.org/aim/article/doi/10.7326/M17-3005