Treatment of immune thrombocytopenia in Australian adults: A multicenter retrospective observational study.

Background: In Australia, prescribing restrictions limit access to internationally recommended second-line therapies such as rituximab and thrombopoietin agonists (TPO-A) (eltrombopag and romiplostim). Subsequent lines of therapy include an array of immunosuppressive and immune-modulating agents directed by drug availability and physician and patient preference. Objectives: The objective of the study was to describe the use of first and subsequent lines of treatment for adult immune thrombocytopenia (ITP) in Australia and to assess their effectiveness and tolerability. Patients/Methods: A retrospective review of medical records was conducted of 322 patients treated for ITP at eight participating centers in Australia between 2013 and 2020. Data were analyzed by descriptive statistics and frequency distribution using pivot tables, and comparisons between centers were assessed using paired t tests. Results: Mean age at diagnosis of ITP was 48.8 years (standard deviation [SD], 22.6) and 58.3% were women. Primary ITP was observed in 72% and secondary ITP in 28% of the patients; 95% of patients received first-line treatment with prednisolone (76%), dexamethasone (15%), or intravenous immunoglobulin (48%) alone or in combination. Individuals with secondary ITP were less steroid dependent (72% vs. 76%) and required less treatment with a second-line agent (47% vs. 58%) in the study sample. Over half (56%) of the cohort received treatment with one or more second-line agents. The mean number of second-line agents used for each patient was 1.9 (SD, 1.2). The most used second-line therapy was rituximab, followed by etrombopag and splenectomy. These also generated the highest rates of complete response (60.3%, 72.1%, and 71.8% respectively). The most unfavorable side effect profiles were seen in long-term corticosteroids and splenectomy. Conclusion: A wide range of "second-line" agents were used across centers with variable response rates and side effect profiles. Findings suggest greater effectiveness of rituximab and TPO-A, supporting their use earlier in the treatment course of patients with ITP across Australia.

Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2.

The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research.

Effects of continuous glucose monitoring on maternal and neonatal outcomes in perinatal women with diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIMS: This systematic review aims to assess the effects of continuous glucose monitoring (CGM) on maternal and neonatal outcomes in perinatal women with diabetes. METHODS: A three-step comprehensive search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. Randomized controlled trials (RCTs) were retrieved from international databases of PubMed, Embase, Cochrane Library, CINAHL, PsycINFO and Scopus from their respective inception dates until 5th January 2021. Comprehensive Meta-Analysis Software Version 3 was used. The overall effect was determined using Hedges' g. Cochrane collaboration's tool version 1 and grading of recommendations, assessment, development and evaluation criteria were used for quality assessment. RESULTS: A total of 1215 records were identified and 10 RCTs involving a total of 1358 perinatal women were selected. The meta-analysis revealed that CGM significantly improved HbA1c levels (g = -0.43, 95% CI: -0.63, -0.22), lowered cesarean section rate (g = -0.17, 95% CI: -0.33, -0.02) and neonatal birth weight (g = -0.16, 95% CI: -0.27, -0.04) when compared to the comparator. The majority (86.67%) has a low risk of biases and certainty of evidence ranged from very low to moderate. CONCLUSION: CGM improves maternal and neonatal outcomes. Future studies should use well-designed large-scale trials.

Myeloproliferative neoplasms: Classifications and an approach to diagnosis.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are a group of illnesses that share a tendency to transform into myelofibrosis and acute leukaemias. Their initial presenting symptoms may be non-specific, which can make diagnosis difficult without a structured approach. OBJECTIVE: The aim of the article is to provide general practitioners (GPs) insight into the classification and clinical approach to diagnosis of MPNs. DISCUSSION: An elevated peripheral blood cell count is often among the first presenting features of an MPN. Although MPNs are rare illnesses, the GP is well placed to identify suspicious features and initiate investigations and referral. It is therefore important for GPs to have an approach to differentiating between reactive and neoplastic causes of elevated blood cell counts.

The importance of community and culture for the recruitment, engagement, and retention of Chinese American immigrants in health interventions.

Chinese Americans experience cancer health disparities throughout the entire cancer continuum. Yet, they remain underrepresented in health research in part due to barriers in recruitment, engagement, and retention. This paper describes the strategies that we devised, by drawing upon our experiences with conducting two culturally sensitive cancer intervention studies, to help researchers improve their recruitment and retention rates of Chinese Americans in health research and address the gap in knowledge on intervention research with this population. The first study assessed the efficacy, adoption, and impact of an intervention, delivered by community health workers, to improve adherence to recommended stomach cancer prevention guidelines for at-risk Chinese Americans. The second study evaluated the feasibility and preliminary efficacy of a culturally adapted version of the Expressive Helping intervention for Chinese American cancer patients and survivors. Our main recruitment strategies revolved around building community relationships, developing culturally sensitive materials, and establishing good first impressions with participants. Our main engagement and retention strategies focused on attending to cultural sensitivity, fostering relationships, and using technology. Harnessing the community's inherent strengths and prioritizing cultural understanding is crucial for culturally sensitive health research with Chinese Americans.

The Safety and Feasibility of a Family First Aid Approach for the Management of Postpartum Hemorrhage in Home Births: A Pre-post Intervention Study in Rural Pakistan.

OBJECTIVE: To evaluate the safety and feasibility of a Family First Aid approach whereby women and their families are provided misoprostol in advance to manage postpartum hemorrhage (PPH) in home births. METHODS: A 12-month prospective, pre-post intervention study was conducted from February 2017 to February 2018. Women in their second and third trimesters were enrolled at home visits. Participants and their families received educational materials and were counseled on how to diagnose excessive bleeding and the importance of seeking care at a facility if PPH occurs. In the intervention phase, participants were also given misoprostol and counselled on how to administer the four 200 mcg tablets for first aid in case of PPH. Participants were followed-up postpartum to collect data on use of misoprostol for Family First Aid at home deliveries (primary outcome) and record maternal and perinatal outcomes. RESULTS: Of the 4008 participants enrolled, 97% were successfully followed-up postpartum. Half of the participants in each phase delivered at home. Among home deliveries, the odds of reporting PPH almost doubled among in the intervention phase (OR 1.98; CI 1.43, 2.76). Among those reporting PPH, women in the intervention phase were significantly more likely to have received PPH treatment (OR 10.49; CI 3.37, 32.71) and 90% administered the dose correctly. No maternal deaths, invasive procedures or surgery were reported in either phase after home deliveries. CONCLUSIONS: The Family First Aid approach is a safe and feasible model of care that provides timely PPH treatment to women delivering at home in rural communities.

Acceptability and feasibility of outpatient medical abortion with mifepristone and misoprostol up to 70 days gestation in Singapore.

OBJECTIVES: The aim of the study was to examine the acceptability and feasibility of using a combined regimen of 200 mg mifepristone and 800 µg buccal misoprostol in an outpatient abortion service in Singapore, where mifepristone is not currently registered. STUDY DESIGN: The pilot prospective study enrolled 130 women who sought termination of pregnancies up to 70 days gestation at two public hospitals in Singapore. Women received 200 mg mifepristone to take at the clinic or at home, followed 24 h later by 800 µg buccal misoprostol administered at home. A follow-up visit was scheduled seven to ten days after mifepristone to confirm the outcome of the abortion. The primary outcome was rate of successful abortion and secondary outcomes were women's preference for location of mifepristone administration and satisfaction with the method. RESULTS: The large majority of women (96.8%) had successful abortions without recourse to surgical intervention. Most women (88.2%) chose to take mifepristone at the clinic. Most women reported the side effects as acceptable (68.3%) or neutral (26.0%). Almost all women (94.4%) were very satisfied or satisfied with the method. CONCLUSIONS: Outpatient medical abortion with mifepristone and misoprostol up to 70 days gestation is acceptable and feasible and has the potential to expand available options in Singapore.

Simplified medical abortion screening: a demonstration project.

OBJECTIVES: The objectives were to evaluate the safety and acceptability of outpatient medical abortion in selected women without a pretreatment ultrasound or pelvic examination. STUDY DESIGN: We conducted a prospective case-series study to estimate the incidence of serious adverse events (death, life-threatening event, hospitalization, transfusion or any other medical problem that we judged to be significant), surgical completion of the abortion and satisfaction in women provided with medical abortion without a pretreatment ultrasound or pelvic examination. We enrolled 406 women requesting medical abortion in Moldova, Mexico and the United States. To be eligible, a woman must have been certain that her last menstrual period started within the prior 56days, have had regular menses before the pregnancy, not have used hormonal contraceptives in the prior 2months (in the United States and Mexico) or 3months (in Moldova), have no risk factors for or symptoms of ectopic pregnancy, and not have had an ultrasound or pelvic exam in this pregnancy. One site also excluded women with uterine enlargement on abdominal palpation. Each participant received mifepristone (200mg orally) and misoprostol (400 mcg sublingually in Moldova; 800 mcg buccally at all other sites) and was followed until complete abortion, defined as requiring no further treatment. RESULTS: Of the 365 (90%) participants who provided sufficient follow-up information for analysis, 347 (95%) had complete abortion without additional treatment, 5 (1%) had surgical aspiration, and 10 (3%) had extra misoprostol. Three participants (1%) had serious adverse events; these included two hospital admissions for heavy bleeding managed with aspiration and one diagnosis of persistent gestational sac 19days after enrollment. Most (317, 90%) participants were pleased with omitting the pretreatment ultrasound and pelvic exam. CONCLUSIONS: In this study, medical abortion without screening ultrasound or pelvic exam resulted in no serious adverse events that were likely to have been prevented by those tests and was highly acceptable. IMPLICATIONS: Screening for medical abortion without exam or ultrasound shows promise as a means for increasing access to this service. More research is needed to develop screening criteria that are more inclusive and simpler for clinical use.

Self-assessment of medical abortion outcome using symptoms and home pregnancy testing.

OBJECTIVES: We aimed to evaluate compliance with a strategy to enable medical abortion patients to assess treatment outcome on their own and decide whether to seek clinical follow-up. STUDY DESIGN: We enrolled women undergoing medical abortion with mifepristone and misoprostol at three clinics in the United States. Each participant was instructed to perform a multilevel pregnancy test (MLPT) 7 days after mifepristone ingestion and to contact the clinic immediately if the test indicated a possible ongoing pregnancy or if specified symptoms occurred. A telephone call was scheduled 14 days after mifepristone ingestion to evaluate participants who had not contacted the clinic earlier. RESULTS: Of the 343 enrolled participants, 90 (26%) did not provide sufficient follow-up information for analysis of compliance with instructions. Of the 253 (74%) who did, 218 (86%) implemented the self-assessment strategy as instructed, 20 (7.9%) failed to report a non-reassuring MLPT result, 4 (1.6%) failed to promptly report symptoms that the study clinician subsequently judged to require evaluation, and 11 (4.3%) did not perform the MLPT. We ascertained abortion outcomes for 239 (70%) of the enrolled women, of whom three were diagnosed with ongoing pregnancies. One other participant was hospitalized for bleeding. All four women had implemented the strategy correctly. Of the 219 enrolled participants (64%) who provided opinions, 170 (78%) indicated that most could use the MLPT to decide whether they are "OK" after an abortion. We did not ascertain opinions from 124 enrolled participants (36%). CONCLUSIONS: At least two thirds of enrolled participants correctly implemented a strategy using symptom evaluation and a MLPT to assess their own medical abortion outcomes. No ongoing pregnancies occurred in women documented not to have implemented the strategy as intended. Perceived feasibility of the self-assessment approach was high. Implications Statement The common practice of scheduling a clinical contact after every medical abortion may not be necessary to ensure safety; enabling patients to determine for themselves whether or not a contact is needed can be a reasonable approach.

Effects of Depot Medroxyprogesterone Acetate Injection Timing on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of timing of depot medroxyprogesterone acetate injection on medical abortion outcome and risk of repeat pregnancy within the subsequent 6 months. METHODS: In a multinational randomized trial, we assigned women undergoing medical abortion who wanted depot medroxyprogesterone acetate to administration either with mifepristone (Quickstart group) or after the abortion (Afterstart group). We ascertained abortion outcome, pregnancies, and contraception use over 7 months. RESULTS: From August 2013 to March 2015, we enrolled 461 participants with pregnancy durations of 75 days or less. Of participants included in the abortion outcome analyses, 14 of 220 (6.4%) and 12 of 226 (5.3%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the upper 90% confidence limit on this difference was 4.9%, within our prestipulated 5% noninferiority margin. Ongoing pregnancy after initial abortion treatment was significantly more common in the Quickstart group (8/220 [3.6%]) than in the Afterstart group (2/226 [0.9%]); the difference was 2.7% (90% confidence interval 0.4-5.6%). By 6 months, 5 of 213 (2.3%) and 7 of 217 (3.2%) in the Quickstart and Afterstart groups, respectively, became pregnant (exact log-rank test, P=.64). Use of highly effective contraceptives was significantly more common in the Quickstart group at 31 days (P<.001), but no difference was apparent at 6 months. The Quickstart group was significantly more satisfied with group assignment. CONCLUSION: Depot medroxyprogesterone acetate administration with mifepristone did not appreciably increase the risk of surgery after medical abortion but did increase the risk of ongoing pregnancy. It enhanced patient satisfaction, but we found no evidence that it decreased 6-month risk of repeat pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01902485.

Antenatal haemoglobinopathy screening in Australia.

Haemoglobinopathy screening should be performed in women with microcytic indices, women from high risk ethnic populations and those with unexplained anaemia. Early testing of women and their partners expedites appropriate management prior to and during pregnancy. Haemoglobinopathy screening is a multistep process beginning with a full blood count, ferritin assay, screening tests for haemoglobinopathies (ie, haemoglobin electrophoresis, high performance liquid chromatography, capillary electrophoresis) and assessment of clinical risk. Iron deficiency may obscure the diagnosis of ß-thalassaemia trait. If possible, haemoglobinopathy testing should be performed when the woman is iron-replete. Genetic testing can be offered on the basis of the combined risk of the couple; but turnaround times are lengthy at present, hence the emphasis on early pregnancy or pre-conception screening. Screening processes vary between states and local health districts; a uniform approach to screening and genetic testing with a national registry to record results would improve management of this growing problem.

Effect of Immediate Compared With Delayed Insertion of Etonogestrel Implants on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of insertion of etonogestrel implants with mifepristone compared with after the abortion on the risks of medical abortion failure and repeat pregnancy over the subsequent 6 months. METHODS: In a randomized trial, we assigned patients undergoing medical abortion to receive etonogestrel implants either with the mifepristone (Quickstart group) or after the abortion (Afterstart group). We followed them for 7 months to ascertain abortion outcome, pregnancies, and contraception use. RESULTS: Between September 2013 and August 2014, we enrolled 236 participants in the Quickstart group and 240 in the Afterstart group. To examine abortion failure, we conducted a noninferiority analysis from which we excluded nine participants who had missing outcome data and four with specified protocol violations. Of the rest, 9 of 229 (3.9%) and 9 of 234 (3.8%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the difference of 0.08% (90% confidence interval -3.1% to 3.3%) excluded our prestipulated noninferiority margin of 5 percentage points. Among participants with pregnancy follow-up through 6 months, 1 of 213 (0.5%) and 3 of 208 (1.4%) in the Quickstart and Afterstart groups, respectively, became pregnant within that time; 6-month pregnancy rates did not differ significantly by group (exact log-rank test, P=.28). At enrollment, significantly more participants in the Quickstart group than in the Afterstart group were satisfied with their group assignments (187/236 [79%] compared with 129/240 [54%], respectively; P<.001). CONCLUSION: Insertion of etonogestrel implants with mifepristone did not appreciably increase medical abortion failure risk and it enhanced patient satisfaction, but we found no evidence that it decreased repeat pregnancy rates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01902485.

A Case of an Acquired Factor VIII Inhibitor Complicated by Multiple Treatment-Related Opportunistic Infections and Review of the Literature.

This case report describes a patient with an idiopathic acquired Factor VIII inhibitor and severe bleeding. She was treated with rituximab after failing first-line treatment with steroids and cyclophosphamide. Two months following rituximab treatment, our patient developed a succession of severe opportunistic infections requiring intensive care unit admission. Over a period of 12 weeks she required treatment for Pseudomonas aeruginosa septicaemia, herpes simplex gingivostomatitis and pharyngotonsillitis, clostridium difficile-related diarrhoea, systemic cytomegalovirus infection, pneumocystis jiroveci, and invasive pulmonary aspergillosis lung infections. After significant rehabilitation, the patient was finally discharged following a 5-month admission. This case highlights the complexity of balancing a life-threatening condition with the side effects of treatment. It also raises the issue of routine prophylaxis for immunosuppression in nonmalignant conditions, which will become a common dilemma with the expanding indications for rituximab use.

Constructing hierarchical spheres from large ultrathin anatase TiO2 nanosheets with nearly 100% exposed (001) facets for fast reversible lithium storage.

Synthesis of nanocrystals with exposed high-energy facets is a well-known challenge in many fields of science and technology. The higher reactivity of these facets simultaneously makes them desirable catalysts for sluggish chemical reactions and leads to their small populations in an equilibrated crystal. Using anatase TiO(2) as an example, we demonstrate a facile approach for creating high-surface-area stable nanosheets comprising nearly 100% exposed (001) facets. Our approach relies on spontaneous assembly of the nanosheets into three-dimensional hierarchical spheres, which stabilizes them from collapse. We show that the high surface density of exposed TiO(2) (001) facets leads to fast lithium insertion/deinsertion processes in batteries that mimic features seen in high-power electrochemical capacitors.