Severe pain should be treated with opioid medications, starting with short-acting medications, then titrating the dose and adding long-acting agents as needed. The authors offer a recommended approach to dosing in the Box: Calculating Short- and Long-Acting Opioid Doses.

Neuropathic pain may respond to gabapentin, pregabalin, or certain antidepressants.

Dyspnea can be successfully managed with nonpharmacologic techniques (e.g., breathing training, gait aids, neuroelectrical muscle stimulation, and chest wall vibration). Low-dose morphine (10-20 mg/d) is considered the gold standard pharmacologic treatment for dyspnea. Other opioids may also be considered.

Depression is not a “normal” response to severe illness, and treatment with selective serotonin reuptake inhibitors is often appropriate. In some cases, other agents may have additional beneficial effects (e.g., mirtazapine may increase appetite and improve sleep; tricyclics, duloxetine, and venlafaxine may improve neuropathic symptoms).

This study identifies opioid use as a novel risk factor for IPD, corroborating other evidence that opioid drugs are associated with an increased risk for infection.

The association was strongest for opioids that are long-acting, are potent, or are used in high doses (50-90 morphine milligram equivalents/d).

An editorial notes that, while this observational study cannot confirm causation, the efforts made to limit confounding, and concordant results seen in 2 other studies, make the conclusions plausible.

These meta-analyses, which include 2 new RCTs, show significantly lower rates of recurrent stroke after mechanical closure of PFO in patients presenting with cryptogenic stroke.

Even with this new evidence, it is difficult to accurately estimate the risk–benefit ratio for this procedure, because baseline rates of recurrent stroke are low, and the frequency of adverse events from the procedure is not well-defined.

An editorial suggests that these meta-analyses may lead to a shift toward more PFO closures in patients with cryptogenic stroke, but the optimal selection criteria for the procedure are not discussed.

This study confirms that the risk for thrombotic disease for patients with MPN is significantly increased. The increase in risk is especially notable in patients in the study's youngest (18 to 59 years) age group.

The risk seems to be highest around the time of diagnosis, decreasing thereafter (probably as a result of treatment) but remaining higher than in controls for the duration of follow-up.

An editorial suggests that this new information should result in a renewed interest in modifying traditional thromboembolic risk factors in these patients, and consideration of combinations of anticoagulant, antiplatelet, and anti-inflammatory treatments.

严重疼痛应使用阿片类药物治疗，从短效药物开始，然后滴定剂量并根据需要添加长效药物。作者提供了一种建议的盒子给药方法：计算短效和长效阿片类药物剂量。

神经性疼痛可能对加巴喷丁，普瑞巴林或某些抗抑郁药有反应。

呼吸困难可以通过非药物技术（例如，呼吸训练，步态辅助，神经电肌肉刺激和胸壁振动）成功解决。低剂量吗啡（10-20 mg / d）被认为是呼吸困难的金标准药物治疗。也可以考虑其他阿片类药物。

抑郁症不是对严重疾病的“正常”反应，使用选择性5-羟色胺再摄取抑制剂治疗通常是合适的。在某些情况下，其他药物可能还有其他有益作用（例如，米氮平可能增加食欲并改善睡眠；三环类药物，度洛西汀和文拉法辛可能会改善神经性症状）。

这项研究确定使用阿片类药物是IPD的新危险因素，进一步证实了阿片类药物与感染风险增加相关的其他证据。

对于长效，有效或以高剂量（50-90吗啡毫克当量/天）使用的阿片类药物，这种关联最强。

社论指出，尽管这项观察性研究无法确定因果关系，但为限制混淆而做出的努力以及其他两项研究中得出的一致结果，使结论似乎合理。

这些荟萃分析（包括2个新的RCT）显示，在存在隐源性卒中的患者中，PFO机械闭合后复发性卒中的发生率显着降低。

即使有了这些新证据，也很难准确估计该手术的风险收益比，因为复发性中风的基线发生率较低，而且手术中不良事件的发生频率也没有明确定义。

社论认为，这些荟萃分析可能会导致隐源性卒中患者转向更多的PFO闭合治疗，但未讨论该手术的最佳选择标准。

这项研究证实，MPN患者发生血栓性疾病的风险显着增加。在研究的最小年龄段（18至59岁）的患者中，风险增加尤为明显。

该风险似乎在诊断时最高，此后降低（可能是治疗的结果），但在随访期间仍高于对照组。

社论认为，这些新信息应引起人们对改变这些患者中传统血栓栓塞危险因素的兴趣，并考虑抗凝，抗血小板和抗炎治疗的组合。