Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance. Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported. Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events). Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.     

临床感染病原菌菌种分布及其耐药性分析

目的了解笔者所在医院2008年度临床感染病原菌的菌种分布及其耐药现状。方法用VITEK微生物自动鉴定仪鉴定菌种,纸片扩散法检测临床分离菌对各种抗菌药物的敏感性,判读标准参照当年的CLSI M100文件。结果临床分离的1900株病原菌中革兰阴性杆菌、革兰阳性球菌和真菌所占比例分别为68.42%、18.16%和12.32%。分离率最高的五种病原菌:铜绿假单胞菌、大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌和白色假丝酵母菌,占所有分离病原菌的59.26%,排前20位的病原菌则占到近90%(89.63%)。革兰阴性杆菌仅对亚胺培南、头孢哌酮/舒巴坦、美洛培南、哌拉西林/他唑巴坦的平均耐药率低于30%,铜绿假单胞菌和鲍曼不动杆菌对亚胺培南、美洛培南的耐药率分别28.9%、32.9%和11.6%、24.7%,大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌的ESBL阳性率分别是52.8%、37.2%和34.6%,金黄色葡萄球和凝固酶阴性葡萄球菌中耐甲氧西林株各占44.0%和60.0%,未检出万古霉素中介或耐药的葡萄球菌,检出万古霉素耐药的粪肠球菌和屎肠球菌各1株。念珠菌对氟康唑耐药率接近5%。结论临床感染病原菌构成变化不大,但真菌检出率逐年升高。非发酵菌耐药率最低的是头孢哌酮/舒巴坦,肠杆菌科耐药率最低的是亚胺培南,ESBL的阳性率逐年升高。加强病原菌及其耐药性检测和监测,对病原学诊断及指导合理选用抗生素具重要参考价值。     

3594株病原菌的分布及耐药性研究

目的:了解中山大学附属东华医院2008年临床常见病原菌对常用抗菌药物的耐药情况,为临床合理用药提供参考依据。方法:纸片扩散法(Kirby-Bauer)检测临床分离菌对各种抗菌药物的耐药性,参照2008版CLSI标准判定药敏结果,并用WHONET5.4软件进行统计分析。结果:全年共检出细菌3 594株,其中革兰阳性菌占39.87%,革兰阴性菌占49.67%。前5位的细菌依次为:大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌和凝固酶阴性葡萄球菌。对抗生素耐药性检测结果显示,MRSA检出率为26%,MRCNS检出率为80%;未发现耐万古霉素的葡萄球菌;粪肠球菌和屎肠球菌对高浓度的庆大霉素的耐药率分别为46.2%和48.1%,1株粪肠球菌对万古霉素不敏感,各种肠道杆菌均对亚胺培南敏感;铜绿假单胞菌耐亚胺培南的菌株占15.4%。结论:我院住院患者分离的细菌耐药性比较严重,对多数常用抗菌药物耐药率呈上升趋势。     

How the war on drugs impacts social determinants of health beyond the criminal legal system

There is a growing recognition in the fields of public health and medicine that social determinants of health (SDOH) play a key role in driving health inequities and disparities among various groups, such that a focus upon individual-level medical interventions will have limited effects without the consideration of the macro-level factors that dictate how effectively individuals can manage their health. While the health impacts of mass incarceration have been explored, less attention has been paid to how the “war on drugs” in the United States exacerbates many of the factors that negatively impact health and wellbeing, disproportionately impacting low-income communities and people of colour who already experience structural challenges including discrimination, disinvestment, and racism. The U.S. war on drugs has subjected millions to criminalisation, incarceration, and lifelong criminal records, disrupting or altogether eliminating their access to adequate resources and supports to live healthy lives. This paper examines the ways that “drug war logic” has become embedded in key SDOH and systems, such as employment, education, housing, public benefits, family regulation (commonly referred to as the child welfare system), the drug treatment system, and the healthcare system. Rather than supporting the health and wellbeing of individuals, families, and communities, the U.S. drug war has exacerbated harm in these systems through practices such as drug testing, mandatory reporting, zero-tolerance policies, and coerced treatment. We argue that, because the drug war has become embedded in these systems, medical practitioners can play a significant role in promoting individual and community health by reducing the impact of criminalisation upon healthcare service provision and by becoming engaged in policy reform efforts.

KEY MESSAGES

• A drug war logic that prioritises and justifies drug prohibition, criminalisation, and punishment has fuelled the expansion of drug surveillance and control mechanisms in numerous facets of everyday life in the United States negatively impacting key social determinants of health, including housing, education, income, and employment.
• The U.S. drug war’s frontline enforcers are no longer police alone but now include physicians, nurses, teachers, neighbours, social workers, employers, landlords, and others.
• Physicians and healthcare providers can play a significant role in promoting individual and community health by reducing the impact of criminalisation upon healthcare service provision and engaging in policy reform.

     

移植性肿瘤的自然消退与免疫形成的研究

本文对小鼠移植性肿瘤的自然消退与其免疫形成进行观察,结果表明:自然消退的EAC昆明鼠对肿瘤的再次攻击具有强烈的排斥反应。应用化疗药物RS034(Sodium sald.ofbishemisuccinate of 7β-Hydroxycholesterol)治愈的L_(1210) DBA/2小鼠进行肿瘤再次移植时,同样产生对抗作用。而用化疗药物5-Fu治愈的小鼠没有出现免疫排斥反应。     

我国药品上市后重点监测相关问题的探讨

摘 要为加强我国药品上市后监管力度,保障药品安全,国家食品药品监督管理总局于2011年正式提出了开展重点监测的要求,并于2013年进一步制定了《生产企业药品重点监测工作指南》（征求意见稿）。该指南对我国药品重点监测这一新制度的含义、内容、责任主体、程序、标准等进行了初步规定,以指导药品生产企业规范开展重点监测工作,保障重点监测制度的顺利实施。重点监测制度目前尚处于起步阶段,各界理解存在差异,通过对指南内容进行解读,对重点监测实施中可能存在的相关问题进行探讨,有助于更好地达到重点监测工作的目的和预期效果。     

Fetal growth restriction

Normal fetal growth is determined by the genetically predetermined growth potential and further modulated by maternal, fetal, placental, and external factors. Fetal growth restriction (FGR) is a failure to reach this potential and is clinically suspected if sonographic estimates of fetal weight, size, or symmetry are abnormal. Integration of fetal anatomy assessment, amniotic fluid dynamics, uterine, umbilical, and fetal middle cerebral artery Doppler is the most effective approach to differentiate potentially manageable placenta-based FGR from aneuploidy, nonaneuploid syndromes, and viral infection. Although placental dysfunction results in a multisystem fetal syndrome with impacts on short- and long-term outcome, only cardiovascular and behavioral responses are helpful to guide surveillance and intervention. Early-onset FGR before 34 weeks gestation is readily recognized but challenging to manage as questions about optimal delivery timing remain unanswered. In contrast, near-term FGR provides less of a management challenge but is often missed as clinical findings are more subtle. Once placenta-based FGR is diagnosed, integrating multivessel Doppler and biophysical profile score provides information on longitudinal progression of placental dysfunction and degree of fetal acidemia, respectively. Choosing appropriate monitoring intervals based on anticipated disease acceleration and intervention when fetal risks exceed neonatal risks are the prevailing current management approaches.     

Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990-2006

Objective  To describe the changing demographic profile of diagnosed HIV-infected pregnant women over time and trends in pregnancy outcome, uptake of interventions and mother-to-child transmission.
Design  National surveillance study.
Setting  UK and Ireland.
Population  Diagnosed HIV-infected pregnant women, 1990–2006.
Methods  Active surveillance of obstetric and paediatric HIV conducted through the National Study of HIV in Pregnancy and Childhood.
Main outcome measures  Maternal characteristics, pregnancy outcome, use of antiretroviral therapy, mode of delivery and mother-to-child transmission.
Results  A total of 8327 pregnancies were reported, increasing from 82 in 1990 to 1394 in 2006, with an increasing proportion from areas outside London. Injecting drug use as the reported risk factor for maternal HIV acquisition declined from 49.2% (185/376) in 1990–1993 to 3.1% (125/4009) in 2004–2006 ( P < 0.001), while the proportion of women born in sub-Saharan Africa increased from 43.5% (93/214) in 1990–1993 to 78.6% (3076/3912) in 2004–2006 ( P < 0.004). Reported pregnancy terminations decreased from 29.6% (111/376) in 1990–1993 to 3.4% (135/4009) in 2004–2006 ( P < 0.001). Most (56.4%, 3717/6593) deliveries were by elective caesarean section, with rates highest in 1999 (66.4%, 144/217). Vaginal deliveries increased from 16.6% (36/217) in 1999 to 28.3% (321/1136) in 2006 ( P < 0.001). Use of antiretroviral therapy in pregnancy increased over time, reaching 98.4% (1092/1110) in 2006, and the overall mother-to-child transmission rate declined from 18.5% (35/189) in 1990–1993 to 1.0% (29/2832) in 2004–2006.
Conclusions  The annual number of reported pregnancies increased dramatically between 1990 and 2006, with changing demographic and geographic profiles and substantial changes in pregnancy management and outcome.