Daily Ards Research Analysis
Across three impactful studies, a large population-based cohort disentangles the contribution of parental infertility versus assisted reproduction procedures to adverse perinatal outcomes, a national dialysis cohort identifies higher sudden cardiac death risk with new haloperidol use compared to chlorpromazine, and a multi-hospital review of dengue fatalities in Nepal details critical care complications including ARDS. Together, these works inform counseling, prescribing, and triage strategies.
Summary
Across three impactful studies, a large population-based cohort disentangles the contribution of parental infertility versus assisted reproduction procedures to adverse perinatal outcomes, a national dialysis cohort identifies higher sudden cardiac death risk with new haloperidol use compared to chlorpromazine, and a multi-hospital review of dengue fatalities in Nepal details critical care complications including ARDS. Together, these works inform counseling, prescribing, and triage strategies.
Research Themes
- Perinatal epidemiology and assisted reproduction
- Medication safety in hemodialysis populations
- Severe dengue mortality drivers and critical care complications
Selected Articles
1. Perinatal risks associated with infertility and medically assisted reproduction: a population-based cohort study.
In a statewide cohort of 824,639 singletons, risks of preterm birth, NICU admission, and early-life hospitalization among ART-conceived infants were substantially attenuated when compared to naturally conceived infants of parents with infertility, indicating that underlying infertility drives much of the excess risk. Fresh embryo transfers carried higher risks than frozen transfers, whereas frozen transfers increased LGA risk.
Impact: This study rigorously separates infertility effects from ART procedure effects at population scale, refining risk counseling for patients considering ART. It also provides actionable insights on fresh versus frozen transfer trade-offs.
Clinical Implications: Counsel patients that much of the perinatal risk reflects underlying infertility; optimize treatment selection and perinatal surveillance accordingly. Prefer frozen transfers when appropriate to mitigate preterm risk, while monitoring for LGA after frozen transfer.
Key Findings
- Compared to NC-fertile, ART singletons had higher risks: preterm birth aRD 25.7/1000 (95% CI 21.3–30.0), NICU admission aRD 8.4/1000 (1.2–15.6), and hospital admission within 2 years aRD 24.6/1000 (17.2–32.0).
- These excess risks were markedly reduced versus NC-infertile: preterm birth aRD 9.5/1000 (4.8–14.2), NICU admission aRD −0.7/1000 (−8.0 to 6.6), and hospital admission aRD 10.6/1000 (2.5–18.7).
- Fresh transfers carried higher risks (e.g., preterm birth aRD 33.7/1000 vs NC-fertile), while frozen transfers showed substantially lower risks versus NC-infertile but increased LGA (aRD 28.5/1000, 95% CI 20.5–36.6).
- ICSI and IVF both showed elevated risks versus NC-fertile that diminished versus NC-infertile; stillbirth risk increased versus NC-fertile but attenuated versus NC-infertile.
Methodological Strengths
- Statewide, population-based cohort with very large sample (n=824,639)
- Inverse probability of treatment weighting and dual-comparator design (NC-fertile and NC-infertile)
- Granular subgroup analyses (ICSI vs IVF; fresh vs frozen transfer)
Limitations
- Observational design using administrative data risks misclassification and unmeasured confounding
- Singleton-only analysis; findings may not generalize to multiples
- NC-infertile comparator may have less severe infertility, potentially underestimating infertility’s contribution
Future Directions: Link clinical infertility phenotypes and ART protocols to perinatal outcomes; evaluate targeted interventions (e.g., embryo transfer strategy) in pragmatic trials; explore mechanisms underlying LGA after frozen transfer.
STUDY QUESTION: Are the risks of adverse perinatal outcomes in singletons born from medically assisted reproduction (MAR) mainly associated with underlying parental infertility, or are they primarily linked to the MAR treatments? SUMMARY ANSWER: While MAR-conceived singletons have increased risks of preterm birth, admission to neonatal intensive care unit (NICU), and hospital admission in early life, these risks are mainly associated with the underlying parental infertility that led to the use of MAR technologies. WHAT IS KNOWN ALREADY: Children born from MAR are at increased risk for some adverse perinatal and infant outcomes. However, to what extent this risk is associated with infertility or MAR treatment remains unclear. This knowledge gap arises from the challenge in disentangling the effects of infertility and MAR treatment, given that parental infertility necessitates the use of MAR treatment. STUDY DESIGN SIZE DURATION: This is a statewide longitudinally data-linked population-based cohort study conducted in New South Wales, Australia, involving all singleton infants born (liveborn or stillborn) between 2009 and 2017. PARTICIPANTS/MATERIALS SETTING METHODS: We applied two comparisons to isolate the associations of infertility from its treatment: (i) MAR infants versus naturally conceived infants from fertile parents (NC-fertile), and (ii) MAR infants versus naturally conceived infants from parents who had a history of infertility (NC-infertile). The study cohort consisted of 824 639 singleton infants, of whom 27 796 (3.4%) were conceived through ART and 13 574 (1.6%) through ovulation induction/intrauterine insemination (OI/IUI), while 783 269 (95.0%) of the infants were naturally conceived (747 018 NC-fertile controls and 36 251 NC-infertile controls). We used the inverse probability of treatment weighting method to make MAR infants comparable with each of the two NC control groups. We then calculated the adjusted risk differences (aRDs) in these propensity score-weighted cohorts. In the subgroup analyses of different forms of ART treatment (ICSI vs IVF and fresh vs frozen embryo transfer), we reweighted the study cohort and compared these subgroups with the two NC control groups separately.
2. Comparative cardiac safety of haloperidol vs. chlorpromazine among people receiving hemodialysis.
In an active-comparator, new-user cohort of hemodialysis patients, initiating haloperidol was associated with a higher 1-year risk of sudden cardiac death than initiating chlorpromazine (aHR 1.38; similar pattern across other cardiac outcomes). Haloperidol was also the most frequently prescribed typical antipsychotic in this population.
Impact: Addresses a critical evidence gap in comparative safety of antipsychotics among hemodialysis patients, a group with very high baseline SCD risk. Findings can directly influence prescribing and monitoring strategies.
Clinical Implications: When antipsychotic therapy is indicated in hemodialysis, prefer agents with lower cardiac risk when feasible; if haloperidol is used, employ ECG/QT monitoring, correct electrolytes, and consider dose minimization. Shared decision-making is warranted.
Key Findings
- Among new users (n=10,225), 1-year SCD incidence was 9.9% with haloperidol vs 5.9% with chlorpromazine.
- Haloperidol initiation was associated with higher 1-year SCD risk vs chlorpromazine: aHR 1.38 (95% CI 1.21–1.59); aRD 2.62% (95% CI −0.27% to 5.51%).
- Similar elevated risks for other adverse cardiac outcomes were observed with haloperidol vs chlorpromazine.
- Haloperidol was the most commonly prescribed typical antipsychotic among U.S. maintenance hemodialysis patients (2007–2019).
Methodological Strengths
- Active comparator, new-user design reducing confounding by indication
- Use of IPTW Fine–Gray competing risk models with ITT approach
- Large, national registry data from the U.S. Renal Data System
Limitations
- Observational design; residual confounding cannot be excluded
- Administrative data may lack clinical detail (e.g., symptom burden, adherence)
- Adjusted risk difference CI included zero, warranting cautious interpretation
Future Directions: Prospective safety studies in dialysis populations, mechanistic work on QT dynamics under uremic conditions, and evaluations of alternative agents or dosing strategies.
BACKGROUND: Sudden cardiac death (SCD) is > 20 times more likely among individuals receiving maintenance hemodialysis, relative to individuals not receiving hemodialysis. Typical antipsychotics increase risk for QT prolongation and SCD in the general population. The comparative cardiac safety of typical antipsychotics among individuals receiving hemodialysis is unknown. METHODS: This cohort study used an active comparator, new-user design to examine relative cardiac safety of the most frequently prescribed oral typical antipsychotics among individuals receiving outpatient maintenance hemodialysis (2007-2019). Data were obtained from the U.S Renal Data System. The primary outcome was 1-year risk of SCD. Inverse probability of treatment weighted Fine and Gray models estimated adjusted hazard ratios (aHR) and adjusted risk differences (aRDs), with 95 % confidence intervals (CIs), using an intention-to-treat approach. In primary analyses, deaths due to causes other than SCD were competing events. RESULTS: Among 846,400 maintenance hemodialysis patients (2007-2019), haloperidol (n = 10,813) and chlorpromazine (n = 5800) were the most commonly prescribed oral typical antipsychotics. Among 6266 haloperidol and 3959 chlorpromazine new-users, 662 (9.9 %) and 234 (5.9 %), respectively, experienced SCD by 1-year. Compared to chlorpromazine new-use, Haloperidol new-use was associated with higher 1-year risk of SCD, aHR (95 % CI) = 1.38 (1.21,1.59); aRD (95 % CI) = 2.62 % (-0.27 %, 5.51 %). Analyses of additional cardiac outcomes yielded similar findings. CONCLUSIONS: Haloperidol was the most prescribed oral typical antipsychotic. Haloperidol new-use associated with a higher 1-year risk of SCD and other adverse cardiac outcomes compared to chlorpromazine new-use. Caution and close monitoring are warranted when newly prescribing haloperidol to individuals receiving hemodialysis.
3. Retrospective analysis of dengue-related fatalities in Nepal, 2022.
Among 88 dengue-related deaths in Nepal across 23 hospitals, critical complications prior to death included septic shock (26%), MODS (23%), cardiopulmonary arrest (20%), and ARDS (15%). Fatalities disproportionately involved older adults with comorbidities and co-infections; late presentation and rapid deterioration were common.
Impact: Provides multi-center, outbreak-period mortality profiling to guide early recognition, referral, and resource allocation in dengue, including the burden of ARDS and shock.
Clinical Implications: Prioritize early diagnosis and timely referral for high-risk patients (older age, comorbidities, co-infections). Prepare ICU capacity for shock, MODS, and ARDS; enhance public awareness of warning signs to reduce late presentation.
Key Findings
- Among 88 deaths, males 53.4% and females 46.6%.
- Pre-terminal complications: septic shock 26%, MODS 23%, cardiopulmonary arrest 20%, ARDS 15%, severe GI bleeding 5%.
- Attribution: severe dengue 52%, dengue with other diseases 26%, dengue with comorbidity complications 22%.
- Older adults with comorbidities and co-infections were disproportionately affected; late presentation and rapid deterioration were common.
Methodological Strengths
- Nationwide surveillance-linked, multi-center case review (23 hospitals)
- Systematic abstraction of medical records during a defined outbreak window
Limitations
- Retrospective design with potential reporting and selection biases
- Limited sample size (n=88) and restricted to reported deaths
- Lack of a control group limits causal inference
Future Directions: Prospective surveillance with standardized severity metrics, early warning triage tools, and evaluation of referral pathways to reduce pre-terminal deterioration.
Dengue is a mosquito-borne acute febrile illness, also known as break bone fever, and is a major public health problem in the tropics and subtropics worldwide. Understanding the factors that contribute to dengue-related mortalities is crucial for decision-making and implementing effective strategies for prompt patient care. This retrospective analysis aimed to understand the clinical characteristics as well as associated infections and co-morbidities related to dengue fatalities in Nepal. Additionally, this insight aids in developing targeted public health interventions to save lives, enhancing disease surveillance systems, and fostering community awareness about dengue prevention. We conducted a retrospective study of the dengue-related deaths in Nepal reported to the Epidemiology and Disease Control Division between 01 January and 30 November 2022 through early warning and reporting system. Medical records of 88 patients who died from dengue were collected and reviewed from 23 hospitals of Nepal. Among 88 deaths that were reviewed, 47 (53.4%) were males and 41 (46.6%) were females. Of all the death cases reviewed, 26% experienced septic shock, 23% had multiple organ dysfunction syndromes, 20% had a cardiopulmonary arrest, 15% had acute respiratory distress syndrome, and 5% had severe gastro-intestinal bleeding, before the death. Fatality from severe dengue were in 46 cases (52%), from dengue associated with other diseases were in 23 cases (26%), and from dengue associated with co-morbidity complications were in 19 cases 22%. Dengue-related mortality in Nepal disproportionately affected older adults with underlying health conditions and co-infections. Late presentation and rapid clinical deterioration were common. Strengthening early diagnosis, timely referral, and clinical management, particularly for high-risk groups is essential. Public awareness of dengue warning signs and prompt healthcare-seeking behavior should be a key component of dengue control strategies.