PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

The success of Australia’s ‘No Jab,No Pay’ policy at a local level; retrospective clinical audit of a single medical practice assessing incidence of catch-up vaccinations

Vaccination is a vital health care initiative to prevent individual and population infection. To increase vaccination rates the federal government implemented the ‘No Jab, No Pay’ policy, where eligibility for several government benefits required children to be fully vaccinated by removing ‘conscientious objections’ and expanding the age range of children whose families receive benefits. This study assesses the impact of this policy at a local area within a single medical practice community in NSW, Australia. A retrospective clinical audit was performed between 2012 and 2017 on a single general practice's vaccination records for children ≤19 years. Catch-up vaccinations were assessed based on age at vaccination. Incidence of catch-up vaccinations was assessed for each of four years before and two years after the implementation of the ‘No Jab, No Pay’ policy in January 2016, along with the age of children and vaccination(s) given. Catch-up vaccinations were assessed temporally either side of implementation of ‘No Jab, No Pay’. Comparing the average annual vaccination catch-up incidence rate of 6.2% pre-implementation (2012–2015), there was an increase to 9.2% in 2016 (p < .001) and 7.8% in 2017 (p = .027). Secondary outcome measurement of catch-up vaccination incidence rates before (2012–2015) and after (2016–2017) ‘No Jab, No Pay’ implementation showed statistically significant increases for children aged 8–11 years (3.2%–5.6%, p = .038), 12–15 years (7.5%–14.7%, p < .001) and 16–19 years (3.3%–10.2%, p < .001) along with a statistically significant reduction in children aged 1–3 years (11.4%–6.2%, p = .015). Also, catch-up rates for DTPa significantly increased after program implementation. This study demonstrates that the Australian federal government vaccination policy ‘No Jab, No Pay’ was coincident with an increase in catch-up vaccinations within a rural NSW community served by one medical practice, especially for older children.     

Education Outcomes of Children Born Late Preterm: A Retrospective Whole-Population Cohort Study

Maternal and Child Health Journal - Early life exposures can have an impact on a child’s developmental trajectory and children born late preterm (34–36&nbsp;weeks gestational age)...