Regulatory review time and pharmaceutical research and development

In the United States, all newly developed drugs undergo a lengthy review process conducted by the US Food and Drug Administration (FDA). These regulatory delays have direct immediate costs for drug manufacturers and patients waiting for treatment. Under certain market conditions, regulatory delays may also affect future research and development (R&D) strategies of pharmaceutical companies. To estimate the magnitude of this effect, we match data on drugs in the development pipeline in 2006 to data that we collect on FDA review times for all drugs approved between 1999 and 2005. Employing a rich and novel set of controls that affect drug R&D decisions and, potentially, regulatory review lags, we find that on average, three additional months of delay result in one fewer drug in development in that drug category. Our results suggest that the length of the regulatory delay matters for pharmaceutical firms' R&D decisions and that the firms are likely unable to pass on these costs onto consumers.     

Respuesta rápida a COVID-19, estrategias de escalada y desescalada para ajustar la capacidad suplementaria de camas de UVI a una epidemia de gran magnitud

BackgroundA major challenge during the COVID-19 outbreak is the sudden increase in ICU bed occupancy rate. In this article we reviewed the strategies of escalation and de-escalation put in place at a large university hospital in Madrid during the COVID-19 outbreak, in order to meet the growing demand of ICU beds.Materials and methodsThe data displayed originated from the hospital information system and the hospital contingency plan.ResultsThe COVID-19 outbreak produced a surge of ICU patients which saturated the available ICU capacity within a few days. A total of four new ICUs had to be opened in order to accommodate all necessary new ICU admissions. Management challenges included infrastructure, material allocation and ICU staffing. Through the strategies put in place the hospital was able to generate a surge capacity of ICU beds of 340%, meet all requirements and also maintain minimal surgical activity.ConclusionsHospital surge capacity is to date hardly quantifiable and often has to face physical limitations (material, personnel, spaces). However an extremely flexible and adaptable management strategy can help to overcome some of these limitations and stretch the system capacities during times of extreme need.     

Transient decrease in sound tolerance levels following hearing deprivation in normal-hearing subjects

ObjectiveTo determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects.DesignParticipants underwent bilateral earplugging before completion of anthropometry, the author's developed questionnaire, the Hamilton Anxiety and Depression Inventory, pure tone audiometry (PTA), stapedial reflex thresholds (SRT), distortion products otoacoustic emissions input/output (DPOAE-I/O), and uncomfortable loudness levels (ULLs). Afterward, the participants were randomly divided into group A, starting at 8:00 a.m. and finishing at 8:00 p.m., and group B, starting at 4:00 p.m. and ending at 4:00 a.m. Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured.Study sampleThirty healthy volunteers.ResultsPTA was 2.68 and 3.33 dB HL in groups A and B, respectively, with no statistical difference between them. ULLs were significantly lower in group A compared to group B, with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B (p < 0.0001). A SRT shift was observed in group A, with no difference in group B, and a night shift in DPOAE-I/O in group B.ConclusionsReduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime; this may be due to increased central gain in the awake cortex.     

一氧化氮治疗吸入性损伤肺动脉高压量效关系的实验研究

目的探讨吸入不同浓度一氧化氮（ＮＯ）治疗兔烟雾吸入性损伤肺动脉高压的量效关系。方法用右心导管检查术连续测定血流动力学指标,观察吸入体积分数为（１、５、１０、２０、３０、４０、５０、６０）×１０－６的ＮＯ对１５只兔烟雾吸入所致肺动脉高压血流动力学的作用。结果吸入（１、５）×１０－６的ＮＯ对平均肺动脉压（ｍＰＡＰ）、肺毛细血管楔压（ＰＣＷＰ）、肺微血管压（Ｐｍｖ）和肺血管阻力（ＰＶＲ）无明显作用（Ｐ＞００５）;吸入（１０、２０、３０、４０、５０、６０）×１０－６的ＮＯ均有降低ｍＰＡＰ、ＰＣＷＰ、Ｐｍｖ的作用（Ｐ＜００５,Ｐ＜００１）;吸入３０×１０－６的ＮＯ即达到最大扩血管效应（Ｐ＜００５,Ｐ＜００１）,再增加吸入ＮＯ的浓度,ＰＶＲ不再进一步降低（Ｐ＞００５）。结论吸入ＮＯ降低烟雾吸入性损伤早期肺动脉压的体积分数以不超过３０×１０－６为宜。     

激素局部注射治疗儿童瘢痕的疗效分析

目的 探讨肾上腺皮质激素(醋酸曲安奈德)局部注射对儿童增生性瘢痕、瘢痕疙瘩的治疗效果及预防瘢痕形成的疗效。方法 对增生性瘢痕、瘢痕疙瘩及预防性注射治疗的患儿473例，共行1514次醋酸曲安奈德局部注射，观察临床效果并进行回顾性分析、评价和总结。结果 增生性瘢痕治疗效果良好，有效率达100％，对关节部位瘢痕的挛缩有明显减轻和预防的作用。瘢痕疙瘩直接注射效果较差，手术切除术后，进行预防性注射可收到良好效果。其余手术后经预防性注射，无增生性瘢痕发生。注射期间28例出现早期Cushings综合征表现，停药半年后消失，随访5年以上，无生长发育异常。结论 小剂量激素局部注射是治疗和预防儿童增生性瘢痕、瘢痕疙瘩的较为安全、可靠、有效的非手术治疗方式之一。     

氯硝安定与安定溶液直肠给药用于惊厥急救的对照研究

目的以安定为对照，探讨氯硝安定溶液直肠给药对惊厥急救的实用价值。方法在２８例儿童中对比观察直肠注入氯硝安定与安定溶液的吸收速度和对脑电活动的影响，并比较两药对大鼠实验性惊厥的疗效。结果氯硝安定与安定溶液均能从直肠迅速吸收，皆于用药５分钟后达有效血浓度，分别于３～８分钟及２～８分钟对脑电活动产生显著影响，明显抑制癫痫样波发放，使美解眠诱发的惊厥致死率从对照组的７０％降为０。结论氯硝安定与安定溶液直肠给药，均能作为小儿惊厥抢救的有效措施。     

腹腔镜下嗜铬细胞瘤切除37例围术期麻醉处理

目的探讨嗜铬细胞瘤围术期合适的麻醉管理。方法术前α1受体阻滞剂、Ca2+通道阻滞剂扩容等准备1~2周;术前30min给予东琅菪碱、安定,37例均采用硬膜外复合气管内全麻。硬膜外起效后开始全麻诱导插管,静注芬太尼、异丙酚、维库溴胺,维持用异丙酚、芬太尼。术中多巴胺、去甲肾上腺、酚妥拉明、硝酸甘油、硝普钠控制血压。术后48h硬膜外自控泵持续镇痛(PCEA)。分析嗜铬细胞患者手术前、中、后麻醉处理。结果术前准备充分,麻醉满意,手术顺利,术后管理得当,镇痛效果确切,患者恢复良好。结论所用麻醉方法、围术期麻醉管理是安全的、合理可行的。