Does newborn screening improve early lung function in cystic fibrosis?

Despite evidence showing an improvement in nutritional outcomes following diagnosis by newborn screening (NBS) for cystic fibrosis (CF), the impact on pulmonary outcomes has been less clear. In this review the approaches to measurement of early lung function and knowledge gained from NBS CF cohorts will be described. Studies which have compared outcomes in those diagnosed by NBS to those diagnosed following symptomatic presentation will be presented. Compiling the evidence base used to evaluate the impact of NBS on pulmonary outcomes has been complicated by improvements in clinical management, infection control practices, as well as public health interventions (such as tobacco smoking bans in public places) that have evolved substantially over recent decades. Forced expiratory volumes have been used as the main outcome but it is important not to draw conclusions for ‘early lung function’ from tests such as spirometry alone, which lack sensitivity in early lung disease. There is, at present, insufficient evidence to draw firm conclusions about the effect of NBS on early lung function. In an era of highly effective treatments targeting the underlying molecular defect responsible for CF, future opportunities for early initiation of treatment may mean that the impact of NBS on early lung function may yet to be realised.     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

Patient navigation across the cancer care continuum: An overview of systematic reviews and emerging literature

Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty-four reviews were quantitative or mixed-methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost-effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost-effectiveness of navigation in screening programs.     

电针联合右美托咪定对骨科老年患者术中应激的影响研究

目的：探讨电针联合右美托咪定对老年骨科患者术中应激的影响。方法：选取拟行手术治疗的老年下肢骨折患者56例为研究对象，采用随机数字表法分为单纯全麻组、电针复合全麻组（简称复合电针组）、右美托咪定复合全麻组（简称复合右美组）及电针联合右美托咪定复合全麻组（简称针药复合组），各14例。记录各组各时间点血压、心率、血氧饱和度等各项监护指标，术前、术后神经心理学指标（简易智力检查评分和疼痛视觉模拟评分）及各时间点血糖水平，术中心血管活性药物使用情况及患者住院天数。结果：术后各时间点针药复合组简易智力检查评分高于单纯全麻组（P＜0.05）；术后72 h内，针药复合组疼痛评分低于其他三组（P＜0.05）；针药复合组术中循环系统指标及血糖水平更稳定；针药复合组术后意识恢复时间最短（P＜0.05）；四组术后呼吸恢复时间与住院天数比较，差异无统计学意义（P＞0.05）；四组心血管活性药物使用率比较，差异无统计学意义（P＞0.05）。结论：老年骨科患者手术中采用电针联合右美托咪定治疗，能够稳定围术期血糖、术中循环系统指标水平，减少术后认知功能障碍发生率，显著降低术中应激水平。     

Effectiveness of typhoid conjugate vaccine against culture-confirmed typhoid in a peri-urban setting in Karachi: A case-control study

BackgroundEnteric fever, caused by Salmonella Typhi and S. Paratyphi, is a cause of high morbidity and mortality among children in South Asia. Rising antimicrobial resistance presents an additional challenge. Typhoid Conjugate Vaccines (TCV) are recommended by the World Health Organization for use among people 6 months to 45 years old living in endemic settings. This study aimed to assess the effectiveness of TCV against culture-confirmed S. Typhi in Lyari Town, Karachi, Pakistan. This peri-urban town was one of the worst affected by the outbreak of extensively drug resistant (XDR) typhoid that started in November 2016.MethodsA matched case-control study was conducted following a mass immunization campaign with TCV at three key hospitals in Lyari Town Karachi, Pakistan. Children aged 6 months to 15 years presenting with culture-confirmed S. Typhi were enrolled as cases. For each case, at least 1 age-matched hospital control and two age-matched community controls were enrolled. Adjusted odds ratios with 95% confidence intervals (CIs) were calculated using conditional logistic regression.ResultsOf 82 typhoid fever patients enrolled from August 2019 through December 2019, 8 (9·8%) had received vaccine for typhoid. Of the 164 community controls and 82 hospital controls enrolled, 38 (23·2%) community controls and 27 (32·9%) hospital controls were vaccinated for typhoid. The age and sex-adjusted vaccine effectiveness was found to be 72% (95% CI: 34% − 88%). The consumption of meals prepared outside home more than once per month (adjusted odds ratio: 3·72, 95% CI: 1·55- 8·94; p-value: 0·003) was associated with the development of culture-confirmed typhoid.ConclusionA single dose of TCV is effective against culture confirmed typhoid among children aged 6 months to 15 years old in an XDR typhoid outbreak setting of a peri-urban community in Karachi, Pakistan.     

HIV Protease: Historical Perspective and Current Research

The retroviral protease of human immunodeficiency virus (HIV) is an excellent target for antiviral inhibitors for treating HIV/AIDS. Despite the efficacy of therapy, current efforts to control the disease are undermined by the growing threat posed by drug resistance. This review covers the historical background of studies on the structure and function of HIV protease, the subsequent development of antiviral inhibitors, and recent studies on drug-resistant protease variants. We highlight the important contributions of Dr. Stephen Oroszlan to fundamental knowledge about the function of the HIV protease and other retroviral proteases. These studies, along with those of his colleagues, laid the foundations for the design of clinical inhibitors of HIV protease. The drug-resistant protease variants also provide an excellent model for investigating the molecular mechanisms and evolution of resistance.