Introduction.-The injection interval for onabotulinumtoxinA (BoNTA) in the management of chronic migraine (CM) is 12 weeks (78-84 days). The aim of this study was to review patient-reported wearing off effect (WOE) of the therapeutic benefit of BoNTA near the end of the treatment cycle. We intended to describe the demographics of patients at baseline and compare groups of patients with multiple episodes of WOE.Methods.-We conducted a retrospective review of patients with CM who . The data from patient-reported WOE (worsening headache variables and neck pain) that occurred during the 4 weeks (28 days) prior to the scheduled re-injection of BoNTA for treatment cycles with injection interval ≤13 weeks and without obvious confounding factors were reviewed.Results.-We identified 98 eligible patients and analyzed 471 treatment cycles. Forty-three unique patients reported at least 1 occurrence of WOE. About 24/43 patients reported 1 WOE event and 19/43 patients reported ≥2 WOE events. Between the 2 groups, anxiety disorder and opioid use for headache were statistically significantly different. In the former group, the median interquartile range (IQR) dose of BoNTA was 165 (155, 175) units and the median IQR duration of the antinociceptive effect of BoNTA was 66.5 (63, 71.5) days. In the latter group, the median IQR dose of BoNTA was 167 (155, 173.3) units and the median IQR duration of the antinociceptive effect of BoNTA was 65.3 (62.5, 68.8) days. Up to 32% of these patients reported an increase in the use of abortive therapies to manage the symptoms of WOE. Discussion.-The primary goal of BoNTA in the treatment of CM is to mitigate the development of central sensitization. Since the 12-week injection paradigm may not provide sustained antinociceptive effect in all patients, it may account for the failure of response to BoNTA. Repeated occurrences of the WOE can potentially lead to medication overuse and impact quality of life.

BACKGROUND: High-flow nasal-cannula (HFNC) may be an oxygen modality useful for preventing invasive mechanical ventilation and mortality; however, its role in acute hypoxemic respiratory failure is not clearly defined. We sought to evaluate the impact of HFNC on mortality across immunocompromised subjects compared to alternative noninvasive oxygen therapies, namely conventional oxygen therapy and noninvasive ventilation (NIV). METHODS: We systematically searched the major databases to identify randomized, controlled trials (RCTs) or observational studies (until May 2018). We included studies reporting the use of HFNC in immunocompromised subjects and evaluated its impact on mortality and invasive mechanical ventilation. RESULTS: Upon review of 6,506 titles, 13 studies (1,956 subjects) fulfilled our inclusion criteria (4 RCTs, 9 observational studies). The predominant cause of immunocompromised status was cancer. Bacterial pneumonia was the most common cause of acute hypoxemic respiratory failure with a median P aO2 /F IO2 of 145 mm Hg (interquartile range 115-175). HFNC was used as the first oxygen strategy in 474 subjects compared to NIV (242 subjects) and conventional O 2 therapy (703 subjects). There was a 46% rate of invasive mechanical ventilation and 36% mortality. Mortality at the longest available follow-up was lower with HFNC compared to the oxygen therapy controls (NIV or conventional O 2 therapy) in 7 studies (1,429 subjects; relative risk 0.72, 95% CI 0.56-0.93, P ‫؍‬ .01). There was a lower rate of invasive mechanical ventilation with HFNC compared to the oxygen therapy controls across 8 studies (1,529 subjects, relative risk 0.81, 95% CI 0.67-0.96, P ‫؍‬ .02). These results were robust across a series of sensitivity analyses. CONCLUSIONS: There exists a need to develop a greater evidence base evaluating the utility of HFNC in immunocompromised subjects. In our exploratory analysis, HFNC was found to decrease mortality and use of invasive mechanical ventilation compared to alternative noninvasive oxygen controls. These results are meant to be exploratory. Higher-quality studies evaluating a more homogeneous population are needed to further elucidate its benefit.

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