The global hearing therapeutic pipeline: 2021

Hearing loss is a serious condition affecting more than 1.5 billion people globally. Many affected people benefit from the use of devices, such as hearing aids, but these do not restore natural hearing, and many users still struggle to follow speech in the presence of background noise. Consequently, there is rapid growth in work to discover therapeutics to address this need. Our analysis of the therapeutic pipeline for inner ear and central processing disorders identified 23 assets in clinical trials and 56 in preclinical development, of which 25% have entered the pipeline in the past three years. The innovative potential of this pipeline is encouraging, but there are translational hurdles to be overcome. We highlight challenges for the pipeline and comment on opportunities to support and strengthen it.     

Measuring healthy female nulliparous pubovisceral muscle from diffusion kurtosis imaging

This study explores the feasibility of using diffusion kurtosis imaging (DKI) in the pelvic floor region and assesses the water diffusivity of the pubovisceral muscle. Twenty-seven healthy young nulliparous females underwent DKI at 3.0 T that included 15 gradient directions and three b values (0, 750, and 1500 s/mm²). The diffusion tensor and diffusion kurtosis metrics values of the pubovisceral muscle were measured after image processing. Two independent sample t-tests, a paired-samples t-test, and a nonparametric hypothesis test were performed as appropriate to compare the differences among different metrics. Twenty-six subjects (mean ± standard deviation age, 25 ± 2 years) were successfully analyzed by measuring the diffusion tensor and diffusion kurtosis metrics of the bilateral pubovisceral muscles. The metrics included mean kurtosis, axial kurtosis, radial kurtosis, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. We found no statistically significant differences for these measurement values between the left and right pubovisceral muscles (p = 0.271–0.931). However, radial kurtosis was greater than axial kurtosis in both pubovisceral muscles (p < 0.001) and axial diffusivity was lower than radial diffusivity in both pubovisceral muscles (p < 0.001). We deem the application of DKI technology to the pelvic floor region to be feasible.     

Integrated Prenatal Care for Women Living With HIV: Primary Care Outcomes in Saskatoon,Saskatchewan

Saskatchewan has the highest rate of new human immunodeficiency virus (HIV) infections in Canada. Of those newly diagnosed, 56% identify as female, 76% identify as Indigenous, and 71% report a history of intravenous drug use. These statistics are strikingly different compared with Canadian data. This brief communication describes prenatal care provided to women living with HIV at an interdisciplinary primary care clinic in Saskatchewan, demonstrating that, despite facing great barriers such as housing insecurity, substance use, and institutionalized racism, women living with HIV can have positive outcomes, including engagement in care and the prevention of perinatal HIV infection.     

Gaslighting in alleged assault ascertained as Munchausen syndrome transcending to malingering in highly counterintuitive self inflicted acid burns

A factitious disorder leading to the self-infliction of highly counter-intuitive burns was diagnosed in a middle-aged female. The injuries were otherwise alleged to have been sustained by assault inflicted upon her by an unknown person. The case was diagnosed by medico-legal interpretation of injuries, in spite of a highly deceptive and concocted history by the patient and her husband. The entity was unique in being associated with magnificent primary, secondary and tertiary gains. The exploitation of the morbid sequel to malinger by the patient, and the involvement of the husband for the prolongation of the illness of his wife for financial gains as gaslighting was highly unusual. The self-infliction of injuries over hands is seen in factitious disorder. However, a combination of a guarded self-immersion of the hands and feet in a corrosive by an illiterate female, followed by malingering to earn livelihood is unprecedented in factitious disorders. The delayed presentation which required amputation of all the limbs to save the life of the patient is a glaring highlight of this case.     

Redefining our protocol of the orthognathic surgery-first approach after 10 years of experience

The objective of this study was to update and redefine some concepts of the surgery-first (SF) approach, regarding its indications and contraindications, virtual planning work-up, surgical tips, and postoperative orthodontic benefits, after 10 years of experience. A retrospective analysis was made of orthognathic surgical procedures following the SF protocol between January 2010 and December 2019 to review inclusion and exclusion criteria, diagnostic workflow, surgical tips, and postoperative outcomes. A total of 148 SF procedures were performed during this period, which corresponded to only 9.2% of the total orthognathic surgeries performed, which means that we have broadened the exclusion criteria instead of reducing them. Surgical tips include interdental corticotomies solely in cases of anterior crowding and leaving the intermaxillary fixation miniscrews in place postoperatively for orthodontic skeletal anchorage. The mean duration of postoperative orthodontic treatment was reduced in comparison to conventional surgery (36.8 vs 87.5 weeks). The overall degree of satisfaction was high not only for the patients, but also for the orthodontists and surgeon. SF is especially indicated for patients who desire an immediate aesthetic result, with short-term orthodontics, or for treatment of sleep-related breathing disorders, if they meet the established criteria.     

北京市精神卫生医务人员对严重精神障碍发病报告制度的认知研究

背景 严重精神障碍发病报告制度作为精神卫生监测的重要一环已运行实施多年，实施效果需要进一步探知。 目的 分析北京市三类精神卫生医务人员对严重精神障碍发病报告制度重要性、主要作用、实施效果、存在问题及完善措施的认知，为促进该制度的完善提供建议。 方法 2019年3—6月，采用方便抽样方法选择234例市级精神专科医院医务人员，采用分层抽样方法选择183例区级精神专科医院医务人员，采用分层抽样方法选择214例社区精神卫生防治医务人员作为研究对象，采用"北京市精神卫生法治状况调查问卷"进行问卷调查，问卷主要内容包括医务人员基本信息及对严重精神障碍发病报告制度的认知。 结果 对于制度重要性，56.3%（103/183）的区级精神专科医院和54.7%（117/214）的社区精神卫生防治医务人员认为其"非常重要"，66.7%（156/234）的市级精神专科医院医务人员认为其"比较重要"。对于主要作用，76.9%（180/234）的市级精神专科医院医务人员和82.7%（177/214）的社区精神卫生防治医务人员认为该制度主要作用为"风险预警"，80.9%（148/183）的区级精神专科医院医务人员认为该制度主要作用为"社区管理"。对于实施效果，44.4%（104/234）的市级精神专科医院医务人员、50.3%（92/183）的区级精神专科医院医务人员和50.9%（109/214）的社区精神卫生防治医务人员认为严重精神障碍发病报告制度实施效果比较好。对于存在问题，77.8%（182/234）的市级精神专科医院医务人员、78.1%（143/183）的区级精神专科医院医务人员和83.2%（178/214）的社区精神卫生防治医务人员认为该制度主要存在的问题为"报告涉及患者隐私信息的收集"。对于完善措施，73.5%（172/234）的市级精神专科医院医务人员和76.6%（164/214）的社区精神卫生防治医务人员认为严重精神障碍发病报告制度完善措施为"规范信息录入、登记、更正、汇总制度"，68.9%（126/183）的区级精神专科医院医务人员认为制度完善措施为"规范信息共享及对患者隐私保护的制度"。 结论 三类医务人员对严重精神障碍发病报告制度的作用及实施效果表示肯定，为实现风险防控与隐私保护并重，兼顾患者管理与服务，应当对该制度予以完善，包括：在法律层面细化相关规定；对患者坚持服务保障与管理并重，完善精神卫生服务体系，落实基本与重大公共卫生服务项目；增加政策宣传力度，提高患者及家属对该制度的认可度。     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.