Morphology combined with HER2 D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping.

AIMS: A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by HER2 dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination. METHODS: Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of HER2 D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus. RESULTS: Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases. CONCLUSIONS: This study validates the use of HER2 D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.

Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption of HER2 D-DISH for ploidy analysis.

AIMS: Diagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to adapt the VENTANA HER2 dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status. METHODS: We selected 25 products of conception, consisting of molar and non-molar cases, to validate the HER2 D-DISH assay. These cases had prior morphological assessment by a perinatal pathologist and ploidy analysis using molecular cytogenetics. Three independent observers, blinded to the original histopathological and genetic diagnosis, scored 10 representative areas on each slide. Interobserver variability was assessed by comparing the total scores of each observer using analysis of variance (ANOVA) and the kappa statistic. RESULTS: Our ploidy scoring system accurately determined the correct number of diploid and triploid conceptuses, demonstrating complete concordance with pre-existing ploidy status and the initial diagnosis. Interobserver agreement between three independent scorers was robust: ANOVA (p=0.36) and kappa statistic (0.812, p<0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p<0.05). Employing our innovative scoring system, known as the 'rule of 5', we established ploidy decision thresholds for all 25 cases. CONCLUSIONS: Our modified HER2 D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The HER2 D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.

Appraisal of hydatidiform mole incidence and registration rates in Ireland following the establishment of a National Gestational Trophoblastic Disease Registry.

AIMS: This study aimed to re-evaluate the incidence of hydatidiform mole (HM) and determine gestational trophoblastic disease (GTD) registration rates in Ireland following the establishment of the National GTD Registry in 2017. METHODS: We performed a 3-year retrospective audit of HM cases (January 2017 to December 2019) reported in our centre. In 2019, we surveyed Irish pathology laboratories to determine the number of HMs diagnosed nationally and compared this data to that recorded in the National GTD Registry. Additionally, we compared both local and national HM incidence rates to those reported internationally. RESULTS: In the 3-year local audit, we identified 87 HMs among 1856 products of conception (POCs) providing a local HM incidence rate of 3.92 per 1000 births. The 1-year pathology survey recorded 170 HMs in 6008 POCs, yielding a national incidence rate of 2.86 per 1000 births. Importantly, the local HM incidence rate exceeded the national incidence rate by 37% and the local partial HM incidence (1 in 296 births) was 64% higher than the nationally incidence rate (1 in 484 births). Notably, 42% of the HM and atypical POCs diagnosed nationally were not reported to the National GTD Registry. CONCLUSIONS: Our study reveals increased HM incidence rates both locally and nationally compared with previous Irish studies. The higher local PHM incidence may reflect more limited access to ploidy analysis in other pathology laboratories nationally. Significantly, almost half of the women with diagnosed or suspected HM were not registered with the National GTD Centre.

Dealing with digital paralysis: Surviving a cyberattack in a National Cancer center.

INTRODUCTION: Cyberattacks represent a growing threat for healthcare delivery globally. We assess the impact and implications of a cyberattack on a cancer center in Ireland. METHODS: On May 14th 2021 (day 0) Cork University Hospital (CUH) Cancer Center was involved in the first national healthcare ransomware attack in Ireland. Contingency plans were only present in laboratory services who had previously experienced information technology (IT) failures. No hospital cyberattack emergency plan was in place. Departmental logs of activity for 120 days after the attack were reviewed and compared with historical activity records. Daily sample deficits (routine daily number of samples analyzed - number of samples analyzed during cyberattack) were calculated. Categorical variables are reported as median and range. Qualitative data were collected via reflective essays and interviews with key stakeholders from affected departments in CUH. RESULTS: On day 0, all IT systems were shut down. Radiotherapy (RT) treatment and cancer surgeries stopped, outpatient activity fell by 50%. hematology, biochemistry and radiology capacity fell by 90% (daily sample deficit (DSD) 2700 samples), 75% (DSD 2250 samples), and 90% (100% mammography/PET scan) respectively. Histopathology reporting times doubled (7 to 15 days). Radiotherapy (RT) was interrupted for 113 patients in CUH. The median treatment gap duration was six days for category 1 patients and 10 for the remaining patients. Partner organizations paused all IT links with CUH. Outsourcing of radiology and radiotherapy commenced, alternative communication networks and national conference calls in RT and Clinical Trials were established. By day 28 Email communication was restored. By day 210 reporting and data storage backlogs were cleared and over 2000 computers were checked/replaced. CONCLUSION: Cyberattacks have rapid, profound and protracted impacts. While laboratory and diagnostic deficits were readily quantified, the impact of disrupted/delayed care on patient outcomes is less readily quantifiable. Cyberawareness and cyberattack plans need to be embedded in healthcare. POLICY SUMMARY: Cyberattacks pose significant challenges for healthcare systems, impacting patient care, clinical outcomes, and staff wellbeing. This study provides a comprehensive review of the impact of the Conti ransomware attack on cancer services in Cork University Hospital (CUH), the first cyberattack on a national health service. Our study highlights the widespread disruption caused by a cyberattack including shutdown of information technology (IT) services, marked reduction in outpatient activity, temporary cessation of essential services such as radiation therapy. We provide a framework for other institutions for mitigating the impact of a cyberattack, underscoring the need for a cyberpreparedness plan similar to those made for natural disasters and the profound legacy of a cyberattack on patient care.

Prevalence, Severity, and Measures of Anxiety in Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: Many studies have reported high rates of anxiety in adults with rheumatoid arthritis (RA). The aim of this systematic review was to examine those findings and determine the overall prevalence, severity, and commonly used measures of anxiety in individuals with RA. METHODS: Six databases were searched from January 2000 without restrictions on language/location, study design, or gray literature. All identified studies that examined anxiety prevalence and severity in adults with RA, as assessed with clinical diagnostic interview and/or standardized self-report measures, were considered for inclusion. Quality assessment of included studies was conducted using a modified Newcastle-Ottawa Evaluation Scale, and the findings were synthesized via a narrative approach. RESULTS: Across the 47 studies (n = 11,085 participants), the sample size ranged from 60 to 1,321 participants with seven studies including healthy controls or groups with other health conditions. The studies were conducted across 23 countries, and anxiety prevalence ranged from 2.4% to 77%, predominantly determined with standardized self-report measures, of which Hospital Anxiety and Depression scale was used most frequently; only eight studies used a clinical diagnostic interview to confirm a specific anxiety diagnosis. Notable associations with anxiety in RA were physical disability, pain, disease activity, depression, and quality of life. CONCLUSION: The reported prevalence of anxiety in RA varied widely potentially because of use of different self-report measures and cutoff points. Such cutoff points will need to be standardized to clinical thresholds to inform appropriate interventions for anxiety comorbidity in RA.

Practical guidelines of the EOTTD for pathological and genetic diagnosis of hydatidiform moles.

Hydatidiform moles are rare and thus most pathologists and geneticists have little experience with their diagnosis. It is important to promptly and correctly identify hydatidiform moles given that they are premalignant disorders associated with a risk of persistent gestational trophoblastic disease and gestational trophoblastic neoplasia. Improvement in diagnosis can be achieved with uniformization of diagnostic criteria and establishment of algorithms. To this aim, the Pathology and Genetics Working Party of the European Organisation for Treatment of Trophoblastic Diseases has developed guidelines that describe the pathological criteria and ancillary techniques that can be used in the differential diagnosis of hydatidiform moles. These guidelines are based on the best available evidence in the literature, professional experience and consensus of the experts' group involved in its development.

Challenges of providing biochemistry results in a patient with Evans syndrome.

A case report of in vivo hemolysis in a female patient with Evans syndrome is described. The patient was admitted with anemia and jaundice and, during her 26-day hospital admission, had 83 samples taken for biochemistry analyses. The laboratory hemolytic index (HI) was frequently elevated due to persistent complement-mediated in vivo hemolysis despite multiple lines of therapy. Initially, the release of many biochemical parameters was blocked per the manufacturer´s recommendations and reported as "sample hemolyzed". The patient developed severe acute kidney injury, ultimately requiring dialysis. Automated and timely reporting of indicative creatinine and other biochemical results in the context of ongoing hemolysis, therefore, became essential to patient care. Following a review of literature from various sources, a laboratory algorithm was designed to ensure the timely release of numerical biochemical values, where possible, with appropriate interpretative comments appended. Biochemistry, hematology, and nephrology teams were in regular communication to ensure patient samples were rapidly identified, analyzed and validated according to the algorithm, informing timely, safe and appropriate patient care. Ultimately, the patient died due to multiple disease- and treatment-related complications. In conjunction with clinical users, laboratories should plan for situations, such as in vivo hemolysis, where significant unavoidable interferences in biochemistry methodologies may occur in an ongoing manner for certain patients. Reporting categorical or best-estimate biochemistry results in such cases can be safer for patients than failing to report any results. Interpretation of these results by clinical teams requires input from appropriately trained and qualified laboratory personnel.

Rare case of steroid cell tumour presenting as resistant hypertension in early pregnancy.

A woman 12 weeks and 3 days pregnant was referred to the emergency department with significant hypertension which, despite aggressive medical management, remained uncontrolled. Markedly elevated levels of renin and aldosterone beyond what is typical in early pregnancy were present, which together with the finding of a right ovarian cyst pointed to the possible diagnosis of an extrarenal reninoma.and the decision was made to perform a right-sided oophorectomy at 16 weeks gestation. Histology demonstrated a staining pattern most consistent with a steroid cell tumour leading to the diagnosis of refractory hypertension secondary to an ovarian steroid cell tumour. Post oophorectomy blood biochemistry rapidly returned to normal, and our patient's hypertension slowly resolved allowing for a large reduction in antihypertensive agent requirements and a successful pregnancy outcome.

Diversity Audit of Medical School Examination Questions.

Phenomenon: This article reports the under-researched presentation of demographic, social, and economic diversity in medical school examination questions. Approach: The present study audited 3,566 pre-clinical and clinical multiple-choice and short answer examination questions in the same year (2018) from three medical schools in two continents to review the diversity of patients portrayed. The audit was based on an extension of Critical Race Theory beyond race and ethnicity to include pertinent social determinants of health. Findings: Patients were presented in 1,537 (43.1%) of the audited examination questions. Apart from age (89.4%) and binary genders (93.9%), other diversity characteristics were rarely portrayed (ethnicity 7.2%, relationship status 1.9%, sexual identity 1.1%, socio-economic status 0.5%, geographic residence 0.1%, disability 0.1%), or not at all (non-binary genders; residency status; religion/spirituality). Insights: While presenting excessive and unnecessary patient characteristics in examination questions should be avoided, the absence of many diversity aspects may reduce examination authenticity and defeat the teaching of diversity in medicine. Medical schools should consider a routine audit and reasonable improvement of the diversity features of patients in examination questions to support teaching and learning activities addressing patients' diversity.

Measurement of hCG in women with Gestational Trophoblastic Disease.

OBJECTIVES: The objective of this study was to collect information on human Chorionic Gonadotrophin (hCG) laboratory testing and reporting in women with Gestational Trophoblastic Disease (GTD), to assess the associated challenges, and to offer perspectives on hCG testing harmonisation. DESIGN: Information was collected from laboratories by electronic survey (Survey Monkey®) using a questionnaire designed by members of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD) hCG Working Party. PARTICIPANTS: The questionnaire was distributed by the EOTTD board to member laboratories and their associated scientists who work within the GTD field. SETTING: The questionnaire was distributed and accessed via an online platform. METHODS: The questionnaire consisted of 5 main sections. These included methods used for hCG testing, quality procedures, reporting of results, laboratory operational aspects, and non-GTD testing capability. In addition to reporting these survey results, examples of case scenarios which illustrate the difficulties faced by laboratories providing hCG measurement for GTD patient management were described. The benefits and challenges of using centralised versus non-centralised hCG testing were discussed alongside the utilisation of regression curves for management of GTD patients. RESULTS: Information from the survey was collated and presented for each section and showed huge variability in responses across laboratories even for those using the same hCG testing platforms. An educational example was presented, highlighting the consequence of using inappropriate hCG assays on clinical patient management (Educational Example A), along with an example of biotin interference (Educational Example B) and an example of high-dose hook effect (Educational Example C), demonstrating the importance of knowing the limitations of hCG tests. The merits of centralised versus non-centralised hCG testing and use of hCG regression curves to aid patient management were discussed. LIMITATIONS: To ensure the survey was completed by laboratories providing hCG testing for GTD management, the questionnaire was distributed by the EOTTD board. It was assumed the EOTTD board held the correct laboratory contact, and that the questionnaire was completed by a scientist with in-depth knowledge of laboratory procedures. CONCLUSIONS: The hCG survey highlighted a lack of harmonisation of hCG testing across laboratories. Healthcare professionals involved in the management of women with GTD should be aware of this limitation. Further work is needed to ensure an appropriate quality assured laboratory service is available for hCG monitoring in women with GTD.

When to consult a geneticist specialising in gestational trophoblastic disease.

BACKGROUND: Gestational trophoblastic disease comprises hydatidiform moles and a rare group of malignancies that derive from trophoblasts. Although there are typical morphological features that may distinguish hydatidiform moles from non-molar products of conception, such features are not always present, especially at early stages of pregnancy. Furthermore, mosaic/chimeric pregnancies and twin pregnancies make pathological diagnosis challenging while trophoblastic tumours can also pose diagnostic problems in terms of their gestational or non-gestational origin. OBJECTIVES: To show that ancillary genetic testing can be used to aid diagnosis and clinical management of GTD. METHODS: Each author identified cases where genetic testing, including short tandem repeat (STR) genotyping, ploidy analysis, next generation sequencing and immunostaining for p57, the product of the imprinted gene CDKN1C, facilitated accurate diagnosis and improved patient management. Representative cases were chosen to illustrate the value of ancillary genetic testing in different scenarios. OUTCOME: Genetic analysis of placental tissue can aid in determining the risk of developing gestational trophoblastic neoplasia, facilitating discrimination between low risk triploid (partial) and high risk androgenetic (complete) moles, discriminating between a hydatidiform mole twinned with a normal conceptus and a triploid conception and identification of androgenetic/biparental diploid mosaicism. STR genotyping of placental tissue and targeted gene sequencing of patients can identify women with an inherited predisposition to recurrent molar pregnancies. Genotyping can distinguish gestational from non-gestational trophoblastic tumours using tissue or circulating tumour DNA, and can also identify the causative pregnancy which is the key prognostic factor for placental site and epithelioid trophoblastic tumours. CONCLUSIONS AND OUTLOOK: STR genotyping and P57 immunostaining have been invaluable to the management of gestational trophoblastic disease in many situations. The use of next generation sequencing and of liquid biopsies are opening up new pathways for GTD diagnostics. Development of these techniques has the potential to identify novel biomarkers of GTD and further refine diagnosis.

Quality improvement project to reduce unplanned extubations in a paediatric intensive care unit.

BACKGROUND: Unplanned extubations are recurrent adverse events in mechanically ventilated children and have been the focus of quality and safety improvement in paediatric intensive care units (ICUs). LOCAL PROBLEM: To reduce the rate of unplanned extubation in the paediatric ICU by 66% (from 2.02 to 0.7). METHODS: This is a quality improvement project that was conducted in a paediatric ICU of a private hospital at the quaternary level. All hospitalised patients who used invasive mechanical ventilation between October 2018 and August 2019 were included. INTERVENTIONS: The project was based on the Improvement Model methodology of the Institute for Healthcare Improvement to implement change strategies. The main ideas of change were innovation in the endotracheal tube fixation model, evaluation of the endotracheal tube positioning, good practices of physical restraint, sedation monitoring, family education and engagement and checklist for prevention of unplanned extubation, with Plan-Do-Study-Act, the tool chosen to test and implement ideas for change. RESULTS: The actions reduced the unplanned extubation rate to zero in our institution and sustained this result for a period of 2 years, totalling 743 days without any event. An estimate was made comparing cases with unplanned extubation and controls without the occurrence of this adverse event, which resulted in savings of R$955 096.65 (US$179 540.41) during the 2 years after the implementation of the improvement actions. CONCLUSION: The improvement project conducted in the 11-month period reduced the unplanned extubation rate to zero in our institution and sustained this result for a period of 743 days. Adherence to the new fixation model and the creation of a new restrictor model, which enabled the implementation of good practices of physical restraint were the ideas of change that had the greatest impact in achieving this result.

"You're actually part of the team": a qualitative study of a novel transitional role from medical student to doctor.

BACKGROUND: Optimizing transitions from final year of medical school and into first post graduate year has important implications for students, patients and the health care system. Student experiences during novel transitional roles can provide insights into potential opportunities for final year curricula. We explored the experiences of medical students in a novel transitional role and their ability to continue learning whilst working as part of a medical team. METHODS: Novel transitional role for final year medical students were created in partnership by medical schools and state health departments in 2020 in response to the COVID-19 pandemic and the need for a medical surge workforce. Final year medical students from an undergraduate entry medical school were employed as Assistants in Medicine (AiMs) in urban and regional hospitals. A qualitative study with semi-structured interviews at two time points was used to obtain experiences of the role from 26 AiMs. Transcripts were analyzed using deductive thematic analysis with Activity theory as a conceptual lens. RESULTS: This unique role was defined by the objective of supporting the hospital team. Experiential learning opportunities in patient management were optimized when AiMs had opportunities to contribute meaningfully. Team structure and access to the key instrument, the electronic medical record, enabled participants to contribute meaningfully, whilst contractual arrangements and payments formalized the obligations to contribute. CONCLUSIONS: The experiential nature of the role was facilitated by organizational factors. Structuring teams to involve a dedicated medical assistant position with specific duties and access to the electronic medical record sufficient to complete duties are key to successful transitional roles. Both should be considered when designing transitional roles as placements for final year medical students.

IGF-2 mediated hypoglycemia and the paradox of an apparently benign lesion: a case report & review of the literature.

BACKGROUND: Non-islet cell tumour hypoglycemia (NICTH) is rarely encountered in clinical practice. Insulin-like growth factor 2 (IGF2) is the most common cause of NICTH observed in the setting of mesenchymal and epithelial neoplasia. This is a paraneoplastic syndrome caused by IGF2 activation of the insulin receptor. CASE PRESENTATION: An 80 year old female presented with a short history of recurrent episodes of confusion with laboratory confirmed hypoglycemia with a plasma glucose of 2.7 mmol/L on fasting which fulfilled Whipple's triad. Diagnostic clues to the aetiology at presentation include the fasting pattern of hypoglycemia, hypokalaemia and the absence of weight gain. A 72 hour fast with results showed early hypoglycemia and suppression of serum insulin, c-peptide, and proinsulin. Serum insulin antibody was not detected. Subsequent measurement of the serum IGF2:IGF1 ratio was elevated at 22.3 and consistent with IGF-2 mediated hypoglycemia and imaging studies demonstrated a pelvic mass. Dietary intervention and oral prednisolone abated hypoglycemia prior to surgery. Ultimately, hypoglycemia resolved following operative intervention and steroid therapy was successfully withdrawn. Histopathology was remarkable for dual neoplastic processes with uterine solitary fibrous tumour (SFT) confirmed as the source of IGF2 hypersecretion on IGF-2 immunohistochemistry and a coincidental invasive high grade serous carcinoma involving the fimbria of the right fallopian tube. CONCLUSION: The paradox in this case is that the benign solitary fibrous tumour accounted for patient morbidity through secretion of IGF2 and without treatment, posed a mortality risk. This is despite the synchronous presence of a highly malignant fallopian tube neoplasm. This case reinforces the need for thorough clinical evaluation of hypoglycemia to allow prompt and definitive management.

Evaluation of Trends in Homeschooling Rates After Elimination of Nonmedical Exemptions to Childhood Immunizations in California, 2012-2020.

Introduction: In 2015, California passed Senate Bill No. 277 (SB 277) and became the first state in more than 30 years to eliminate nonmedical exemptions to mandatory childhood immunizations for school entry. One concern that emerged was that the law created an incentive for parents to remove children from brick-and-mortar schools to bypass the immunization requirements. Objective: To assess the trends in homeschooling rates after the elimination of nonmedical exemptions to the requirement of childhood immunizations for school entry. Design, Setting, and Participants: This preintervention-postintervention cross-sectional study calculated homeschooling rates as the number of students in kindergarten through grade 8 (K-8) enrolled through each of California's 3 homeschooling mechanisms (independent study program, private school affidavit, and private school satellite program) divided by all K-8 students enrolled in the same academic year. Data on homeschooling rates were obtained from the California Department of Education. Interrupted time series analyses were conducted using a linear regression model in which the outcome variable was the percentage of students enrolled in a homeschool program before and after SB 277. Data were collected and analyzed from October 3, 2012, to October 2, 2019. Intervention: Passage of SB 277, which eliminated nonmedical exemptions to childhood immunizations for school entry. Main Outcomes and Measures: Homeschooling rates for K-8 students. Results: Among the students included in the analysis, the homeschooling enrollment for K-8 students in California increased from 35 122 students (0.8%) during the 2012-2013 school year to 86 574 students (1.9%) during the 2019-2020 school year; however, the implementation of SB 277 was not associated with an increase in the percentage of students enrolled in homeschooling programs in California beyond the secular trend. The increase in homeschooling was greatest for the lower grade levels: kindergarten homeschooling enrollment increased from 2068 students (0.4%) in the 2012-2013 school year to 10 553 students (1.9%) in the 2019-2020 school year, whereas the grade 8 homeschool enrollment rate increased from 5146 students (1.0%) in the 2012-2013 school year to 10 485 students (2.0%) in the 2019-2020 school year. Independent study programs accounted for 20 149 students (45.3%) of homeschooling enrollment, private school affidavits accounted for 19 333 students (43.5%), and private school satellite programs accounted for 4935 students (11.1%) during the 2015-2016 school year. Conclusions and Relevance: The findings of this study suggest that legislative action to limit nonmedical exemptions for compulsory vaccination for school entry is not associated with removal of students from classroom-based instruction in brick-and-mortar institutions.

Problems with evidence assessment in COVID-19 health policy impact evaluation: a systematic review of study design and evidence strength.

INTRODUCTION: Assessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. METHODS: We included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on 26 November 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation. RESULTS: After 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-sectional), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DISCUSSION: The reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigour to be actionable by policy-makers. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

Advances in the diagnosis and early management of gestational trophoblastic disease.

Gestational trophoblastic disease describes a group of rare pregnancy related disorders that span a spectrum of premalignant and malignant conditions. Hydatidiform mole (also termed molar pregnancy) is the most common form of this disease. Hydatidiform mole describes an abnormal conceptus containing two copies of the paternal genome, which is classified as partial when the maternal genome is present or complete when the maternal genome is absent. Hydatidiform mole typically presents in the first trimester with irregular vaginal bleeding and can be suspected on ultrasound but confirmation requires histopathological evaluation of the products of conception. Most molar pregnancies resolve without treatment after uterine evacuation, but occasionally the disease persists and develops into gestational trophoblastic neoplasia. Close monitoring of women after molar pregnancy, with regular measurement of human chorionic gonadotrophin concentrations, allows for early detection of malignancy. Given the rarity of the disease, clinical management and treatment is best provided in specialist centres where very high cure rates are achievable. This review looks at advances in the diagnosis and early management of gestational trophoblastic disease and highlights updates to disease classification and clinical guidelines. Use of molecular genotyping for improved diagnostic accuracy and risk stratification is reviewed and future biomarkers for the earlier detection of malignancy are considered.

Community-based Lung Cancer Screening Results in Relation to Patient and Radiologist Characteristics: The PROSPR Consortium.

Rationale: Lung-RADS classification was developed to standardize reporting and management of lung cancer screening using low-dose computed tomographic (LDCT) imaging. Although variation in Lung-RADS distribution between healthcare systems has been reported, it is unclear if this is explained by patient characteristics, radiologist experience with lung cancer screening, or other factors. Objectives: Our objective was to determine if patient or radiologist factors are associated with Lung-RADS score. Methods: In the Population-based Research to Optimize the Screening Process (PROSPR) Lung consortium, we conducted a study of patients who received their first screening LDCT imaging at one of the five healthcare systems in the PROSPR Lung Research Center from May 1, 2014, through December 31, 2017. Data on LDCT scans, patient factors, and radiologist characteristics were obtained via electronic health records. LDCT scan findings were categorized using Lung-RADS (negative [1], benign [2], probably benign [3], or suspicious [4]). We used generalized estimating equations with a multinomial distribution to compare the odds of Lung-RADS 3, and separately Lung-RADS 4, versus Lung-RADS 1 or 2 and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between Lung-RADS assignment and patient and radiologist characteristics. Results: Analyses included 8,556 patients; 24% were assigned Lung-RADS 1, 60% Lung-RADS 2, 10% Lung-RADS 3, and 5% Lung-RADS 4. Age was positively associated with Lung-RADS 3 (OR, 1.02; 95% CI, 1.01-1.03) and 4 (OR, 1.03; 95% CI, 1.01-1.05); chronic obstructive pulmonary disease (COPD) was positively associated with Lung-RADS 4 (OR, 1.78; 95% CI, 1.45-2.20); obesity was inversely associated with Lung-RADS 3 (OR, 0.70; 95% CI, 0.58-0.84) and 4 (OR, 0.58; 95% CI, 0.45-0.75). There was no association between sex, race, ethnicity, education, or smoking status and Lung-RADS assignment. Radiologist volume of interpreting screening LDCT scans, years in practice, and thoracic specialty were also not associated with Lung-RADS assignment. Conclusions: Healthcare systems that are comprised of patients with an older age distribution or higher levels of COPD will have a greater proportion of screening LDCT scans with Lung-RADS 3 or 4 findings and should plan for additional resources to support appropriate and timely management of noted positive findings.