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Background: In 2016, the WHO Classification of Brain Tumors included brain invasion as a standalone diagnostic criterion for grade 2 meningioma diagnosis. In this study we explored the impact of this change on the incidence and distribution of meningioma grades. Methods: All cases of meningiomas diagnosed from 2007-2020 at a tertiary care hospital were identified. The distribution of meningioma grades before (WHO 2007) and after (WHO 2016) the introduction of the 2016 WHO criteria were compared. Each case in the 2007 cohort was re-graded according to the 2016 criteria to determine the intra-class correlation (ICC) between grading criteria. Results: Of 814 cases, 532 (65.4%) were in the 2007 WHO cohort and 282 (34.6%) were in the 2016 WHO cohort. There were no differences in the distribution of meningioma grades between cohorts (p=0.11). Upon re-grading, 21 cases (3.9%) were changed. ICC between original and revised grade was 0.92 (95% CIs: 0.91-0.93). Amongst Grade 2 meningiomas with brain invasion, 75.8% had three or more atypical histologic features or an elevated mitotic index. Conclusions: Brain invasion alone has minimal impact on the incidence or distribution of specific meningioma grade tumors, likely due to cosegregation of grade elevating features.
Background: The coronavirus disease 2019 (COVID-19) pandemic has led the implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 6 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=150 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.
This study aimed to determine the implications of including tympanometry in the Rapid Assessment of Hearing Loss survey protocol. A comparative study design was employed, with findings from otoscopy compared with the results of tympanometry.
A population-based survey of the prevalence and causes of hearing loss among adults aged over 35 years in The Gambia was conducted. Clinical assessments included air conduction audiometry, otoscopy and clinical history. Otoscopy outcome was recorded and for those with hearing loss, a probable cause was assigned. Following otoscopy, tympanometry was completed. Otoscopy outcome was not changed as a result of tympanometry. Clinician assigned cause was compared to the results of tympanometry. The proportion of causes potentially misclassified by excluding tympanometry was determined.
Among people with hearing loss, including tympanometry led to a higher proportion diagnosed with middle-ear conditions.
The value of adding tympanometry to population-based survey protocols is a higher estimated proportion of hearing loss being attributed to middle-ear disease rather than sensorineural causes. This can inform service needs as more people will be classified as needing medical or surgical services, and a slightly lower number will need rehabilitative services, such as hearing assistive devices. It is highly recommended that tympanometry is included in the protocol.
Continuous exposure to stressors can lead to vulnerability and, in some cases, resilience. This study examined the variation in its psychological impact across the first four waves of COVID-19 in Hong Kong.
Transcripts from Open Up, an online text-based counseling service, between January 2019 and January 2021 were analyzed (N = 60 775). We identified COVID-19 mentioned sessions using keywords and further categorized them into those that also mentioned symptoms of common mental disorders (CMDs) and those that did not. Autoregressive integrated moving average models were used to analyze the associations between the severity of the outbreak and the mention of COVID-19 and CMDs.
Results revealed that the pandemic led to increased psychological distress. Compared to prior to its advent, more people sought help in the initial months of the outbreak. Furthermore, associations were found between the severity of the outbreak and the number of help-seeker mentioning the pandemic, as well as between the outbreak severity and the number of help-seekers disclosing psychological distress. However, these relationships were not uniform across the four waves of outbreaks; a dissociation between outbreak severity and help-seekers' concern was found in the fourth wave.
As the pandemic waxes and wanes, people may become habituated to its psychological toll. This may be interpreted as a form of resilience. Instead of worsening with time, the psychological impact of COVID-19 may reduce with repeated exposure.
There is currently limited evidence regarding the potential complications of sphenopalatine artery ligation. The post-operative outcomes at two secondary care centres over a 10-year period were reviewed.
A retrospective review was undertaken of patients undergoing emergency and elective sphenopalatine artery ligation between January 2011 and January 2021. Their demographics, peri-operative care and post-operative outcomes were recorded. The median follow-up time was 54 days (range, 0–2657 days).
Ninety-one patients were included. Four patients (4.4 per cent) had a septal perforation at post-operative review. Nineteen patients (20.9 per cent) had post-operative bleeding that extended their in-patient stay, with five patients (5.5 per cent) requiring revision surgery. Pre-operative non-dissolvable nasal packing was used a median of 1 time (range, 0–8 times).
Further research on outcomes of sphenopalatine artery ligation is needed. Pre-operative non-dissolvable nasal packing, concurrent septal surgical procedures, surgical techniques, and co-morbidities such as hypertension represent potential confounding factors that could not be further assessed in this small, retrospective study.
Background: The coronavirus disease 2019 (COVID-19) pandemic has led an implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 9 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=144 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during the pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.
Deep learning, a subset of artificial intelligence, has shown great potential in several recent applications to pathology. These have mainly involved the use of classifiers to diagnose disease, while generative modelling techniques have been less frequently used. Generative adversarial networks (GANs) are a type of deep learning model that has been used to synthesize realistic images in a range of domains, both general purpose and medical. In the GAN framework, a generator network is trained to synthesize fake images, while a dueling discriminator network aims to distinguish between the fake images and a set of real training images. As GAN training progresses, the generator network ideally learns the important features of a dataset, allowing it to create images that the discriminator cannot distinguish from the real ones. We report on our use of GANs to synthesize high resolution, realistic histopathology images of gliomas. The well- known Progressive GAN framework was trained on a set of image patches extracted from digital slides in the Cancer Genome Atlas repository, and was able to generate fake images that were visually indistinguishable from the real training images. Generative modelling in pathology has numerous potential applications, including dataset augmentation for training deep learning classifiers, image processing, and expanding educational material.
This presentation will enable the learner to:
1. Explain basic principles of generative modelling in deep learning.
2. Discuss applications of deep learning to neuropathology image synthesis.
Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension.
We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007–December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011–2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430–437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified.
In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03–1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00–1.67).
Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.
Several questions still exist in the literature on the relationship between cumulative exposure to work-related incidents and posttraumatic stress disorder (PTSD) in First Responders (FR).
To address three unanswered questions in the field.
(1) Are different cumulative exposure scoring algorithms similarly related to PTSD?
(2) Is PTSD associated only with incidents rated as severe and traumatic?
(3) Can we identify cut-off scores of cumulative exposure that maximize sensitivity and specificity to predict PTSD?
To better characterize the relationship between cumulative exposure and PTSD in FR.
The association between exposure and PTSD was examined with logistic and linear regression and with receiver operating characteristic analysis in 349 FR.
(1) The strength of the association between PTSD and total cumulative exposure indexes varied across different scoring algorithms.
(2) Compared to total cumulative exposure indexes and to sub-scores of exposure to non-traumatic and/or less severe incidents, sub-scores indexing exposure to severe traumatic events only were more strongly and significantly associated with PTSD.
(3) The use of two cut-off scores maximizes sensitivity and specificity to predict PTSD.
(1) The relationship between current PTSD and cumulative exposure is partially dependent on the approach used to quantify exposure.
(2) Focusing on the assessment of cumulative exposure to severe traumatic events is sufficient to predict PTSD, and might be more useful and effective in research and clinical decision-making.
(3) Sensitivity and specificity of exposure scores might help improve secondary prevention (early detection and effective intervention) of individuals at risk.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1. Explore the current molecular landscape of pediatric high grade gliomas
2. Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3. Discuss the current status of NTRK inhibitor clinical trials
There have been significant changes in the diagnostic criteria for diffuse gliomas in the 2016 WHO CNS tumor classification, with the incorporation of molecular criteria into a number of definitions. This has placed a greater emphasis on the availability of key immunohistochemical and molecular tests. In order to determine the effect that these changes have had on neuropathology practice and the access of different centres to these tests, we designed a survey that was sent to all members of the Canadian Association of Neuropathology member list in the fall of 2017. This survey asked a number of questions relating to the approach to glioma diagnosis, immunohistochemical/molecular test ordering patterns, in-house test availability, and need to send out for testing. In this presentation we will present preliminary results from this survey, with a focus on institutional testing capabilities. This provides a valuable resource that could ultimately need to a national database of immunohistochemical and molecular test availability for each neuropathology centre.
This presentation will enable the learner to:
1. Review the key molecular markers in the diagnosis of adult gliomas and methods of testing for them
2. Discuss the effect that the 2016 WHO CNS tumor update has had on clinical practice in Canada
Introduction: A significant gap exists between the number of people waiting for an organ and donors. There are currently 1,628 people awaiting organ donation in Ontario alone. In 2018 to date, 310 donors have donated 858 organs. The purpose of this study was to determine whether there were missed donors in the Emergency Department (ED) and by what percent those missed donors would increase organ donation overall. Methods: This was a health records and organ donation database review of all patients who died in the ED at a large academic tertiary care center with 2 campuses and 160,000 visits per year. Patients were included from November 1, 2014 – October 31, 2017. We collected data on demographics, cause of death, and suitability for organ donation. Data was cross-referenced between hospital records and the provincial organ procurement organization called Trillium Gift of Life Network (TGLN) to determine whether patients were appropriately referred for consideration of donation in a timely manner. Potential missed donors were manually screened for suitability according to TGLN criteria. We calculated simple descriptive statistics for demographic data and the primary outcome. The primary outcome was percentage of potential organ donors missed in the Emergency Department (ED). Results: There were 606 deaths in the ED from November 1, 2014 – October 31, 2017. Patients were an average of 71 years old, 353 (58%) were male, and 75 (12%) died of a traumatic cause. TGLN was not contacted in 12 (2%) of cases. During this period there were two donors from the ED and 92 from the ICU. There were ten missed potential donors. They were an average of 67 years, 7 (70%) were male, and 2 (20%) died of a traumatic cause. In all ten cases, patients had withdrawal of life sustaining measures for medical futility prior to TGLN being contacted for consideration of donation. There could have been an addition seven liver, six pancreatic islet, four small bowel, and seven kidney donors. The ten missed ED donors could have increased total donors by 11%. Conclusion: The ED is a significant source of missed organ donors. In all cases of missed organ donation, patients had withdrawal of life sustaining measures prior to TGLN being called. In the future, it is essential that all patients have an organ procurement organization such as TGLN called prior to withdrawal of life sustaining measures to ensure that no opportunity for consideration of organ donation is missed.
Introduction: Low acuity patients have been controversially tagged as a source of emergency department (ED) misuse. Authorities for many Canadian health regions have set up policies so these patients preferably present to walk-in clinics (WIC). We compared the cost and quality of the care given to low acuity patients in an academic ED and a WIC of Québec City during fiscal year 2015-16. Methods: We conducted an ambidirectional (prospective and retrospective) cohort study using a time-driven activity-based costing method. This method uses duration of care processes (e.g., triage) to allocate to patient care all direct costs (e.g., personnel, consumables), overheads (e.g., building maintenance) and physician charges. We included consecutive adult patients, ambulatory at all time and discharged from the ED or WIC with a diagnosis of upper respiratory tract infection (URTI), urinary tract infection (UTI) or low back pain. Mean cost [95%CI] per patient per condition was compared between settings after risk-adjustment for age, sex, vital signs, number of regular medications and co-morbidities using generalized log-gamma regression models. Proportions [95%CI] of antibiotic prescription and chest X-Ray use in URTI, compliance with provincial guidelines on use of antibiotics in UTI, and column X-Ray use in low back pain were compared between settings using a Pearson Chi-Square test. Results: A total of 409 patients were included. ED and WIC groups were similar in terms of age, sex and vital signs on presentation, but ED patients had a greater burden of comorbidities. Adjusted mean cost (2016 CAN$) of care was significantly higher in the ED than in the WIC (p < 0.0001) for URTI (78.42[64.85-94.82] vs. 59.43[50.43-70.06]), UTI (78.88[69.53-89.48] vs. 53.29[43.68-65.03]), and low back pain (87.97[68.30-113.32] vs. 61.71[47.90-79.51]). For URTI, antibiotics were more frequently prescribed in the WIC (44.1%[34.3-54.3] vs. 5.8%[1.2-16.0]; p < 0.0001) and chest X-Rays, more frequently used in the ED (26.9%[15.6-41.0] vs. 13.7%[7.7-22.0]; p = 0.05). No significant differences were observed in the compliance with guidelines on use of antibiotics in UTI and in the use of column X-Ray in low back pain. Conclusion: Total cost of care for low acuity patients is lower in walk-in clinics than in EDs. However, our results suggest that quality-of-care issues should be considered in determining the best alternate setting for treating ambulatory emergency patients.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
The classification system for gliomas has undergone significant revisions in the last several years, with the incorporation of molecular criteria and removal of mixed histologic diagnoses. Large-scale molecular studies have elucidated the biological characteristics of low grade gliomas, and enabled grouping based on IDH mutational and 1p19q codeletion status that outperforms histology in predicting patient outcomes. Mutations in ATRX and TP53 are largely mutually exclusive of 1p19q- codeletion in the context of mutant IDH, and are useful in screening patients for further molecular studies.
At our institution, new testing methods for 1p19q codeletion and ATRX were implemented in 2014, and in this presentation we review all cases submitted for 1p19q testing since this time. In comparing histologic to molecular diagnoses, the majority of histologic oligodendrogliomas indeed have 1p19q codeletion, while oligoastrocytomas and GBMOs largely are re-classified as astrocytomas and glioblastomas, respectively. We have also found that loss of ATRX nuclear expression associated with ATRX mutation is highly indicative of 1p19q retention, however the immunohistochemical test can be challenging to interpret and there have been a small number of discordant results.
Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.
There has recently been an increased interest in mental health indicators for the monitoring of population wellbeing, which is among the targets of Sustainable Development Goals adopted by the United Nations. Levels of subjective wellbeing and suicide rates have been proposed as indicators of population mental health, but prior research is limited.
Data on individual happiness and life satisfaction were sourced from a population-based survey in Hong Kong (2011). Suicide data were extracted from Coroner's Court files (2005–2013). Area characteristic variables included local poverty rate and four factors derived from a factor analysis of 21 variables extracted from the 2011 census. The associations between mean happiness and life satisfaction scores and suicide rates were assessed using Pearson correlation coefficient at two area levels: 18 districts and 30 quantiles of large street blocks (LSBs; n = 1620). LSB is a small area unit with a higher level of within-unit homogeneity compared with districts. Partial correlations were used to control for area characteristics.
Happiness and life satisfaction demonstrated weak inverse associations with suicide rate at the district level (r = −0.32 and −0.36, respectively) but very strong associations at the LSB quantile level (r = −0.83 and −0.84, respectively). There were generally very weak or weak negative correlations across sex/age groups at the district level but generally moderate to strong correlations at the LSB quantile level. The associations were markedly attenuated or became null after controlling for area characteristics.
Subjective wellbeing is strongly associated with suicide at a small area level; socioeconomic factors can largely explain this association. Socioeconomic factors could play an important role in determining the wellbeing of the population, and this could inform policies aimed at enhancing population wellbeing.
Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.
In recent years, various pro-natalist policies have been adopted in Singapore and other high-income Asian countries with low fertility, aiming at raising fertility rates. Previous studies were mainly focused on the impact or outcome of the policies. This paper, however, aims to identify the most influential groups in determining Singapore's total fertility rate (TFR) and evaluate the targeting of pro-natalist measures adopted by the government. We first reveal the changing age-parity-and-marital-status composition of women at childbearing age, and further conduct an elasticity analysis to assess the roles of different subgroups of women in changing the TFR. Our results show that compared to other groups, the 20–29-year-old single women and the married childless women aged 30–34 (‘married’ throughout this paper includes women who are or have been married) are more influential in determining the TFR and should be the potential pro-natalist target groups. However, Singapore's pro-natalist policies are more in favour of third and higher-order births. Such mismatch indicates that, if more efforts are devoted to facilitating marriage and first births in these potential groups, the TFR may be increased effectively. In order to achieve a long-term and significant fertility reversal, it calls for a long-term and integrated policy package.