Lauren E. Cipriano

• Hafeez, A.; Cipriano, L. E.; Kim, R. B.; Zaric, G. S.; Schwarz, U. I.; Sarma, S., 2024, "Cost-Effectiveness Analysis of Pharmacogenomics (PGx)-Based Warfarin, Apixaban, and Rivaroxaban Versus Standard Warfarin for the Management of Atrial Fibrillation in Ontario, Canada", PharmacoEconomics, January 42(1): 69 - 90.
  Abstract: To assess the cost-effectiveness of pharmacogenomics (PGx)-based warfarin (i.e., warfarin dosing following genetic testing), apixaban, and rivaroxaban oral anticoagulation versus standard warfarin for the treatment of newly diagnosed patients with nonvalvular atrial fibrillation (AF) aged ≥ 65 years.

  Link(s) to publication:

  https://doi.org/10.1007/s40273-023-01309-z

  http://dx.doi.org/10.1007/s40273-023-01309-z

• Goldhaber-Fiebert, J.; Cipriano, L. E., 2023, "Pricing Treatments Cost-Effectively when They Have Multiple Indications: Not Just a Simple Threshold Analysis", Medical Decision Making, October 43(7-8): 914 - 929.
  Abstract: Economic evaluations of treatments increasingly employ price-threshold analyses. When a treatment has multiple indications, standard price-threshold analyses can be overly simplistic. We examine how rules governing indication-specific prices and reimbursement decisions affect value-based price analyses.

  Link(s) to publication:

  https://journals.sagepub.com/doi/10.1177/0272989X231197772

  http://dx.doi.org/10.1177/0272989X231197772

• Tran, C.; Cipriano, L. E.; Driman, D. K., 2023, "Impact of COVID-19-related health care disruptions on pathologic cancer staging during the first pandemic year: a retrospective cohort study from March 2018 to March 2021", CMAJ Open, May 11(3): E475 - E484.
  Abstract: Background: The COVID-19 pandemic has created major disruptions in cancer care, with reductions in diagnostic tests and treatments. We evaluated the impact of these health care–related changes on cancer staging by comparing cancers staged before and during the pandemic. Methods: We performed a retrospective cohort study at London Health Sciences Centre and St. Joseph’s Health Care London, London, Ontario, Canada. We evaluated all pathologically staged breast, colorectal, prostate, endometrial and lung cancers (the 5 most common cancers by site, excluding nonmelanoma skin cancer) over a 3-year period (Mar. 15, 2018–Mar. 14, 2021). The pre-COVID-19 group included procedures performed between Mar. 15, 2018, and Mar. 14, 2020, and the COVID-19 group included procedures performed between Mar. 15, 2020, and Mar. 14, 2021. The primary outcome was cancer stage group, based on the pathologic tumour, lymph node, metastasis system. We performed univariate analyses to compare demographic characteristics, pathologic features and cancer stage between the 2 groups. We performed multivariable ordinal regression analyses using the proportional odds model to evaluate the association between stage and timing of staging (before v. during the pandemic). Results: There were 4055 cases across the 5 cancer sites. The average number of breast cancer staging procedures per 30 days increased during the pandemic compared to the yearly average in the pre-COVID-19 period (41.3 v. 39.6), whereas decreases were observed for endometrial cancer (15.9 v. 16.4), colorectal cancer (21.8 v. 24.3), prostate cancer (13.6 v. 18.5) and lung cancer (11.5 v. 15.9). For all cancer sites, there were no statistically significant differences in demographic characteristics, pathologic features or cancer stage between the 2 groups (p > 0.05). In multivariable regression analysis, for all cancer sites, cases staged during the pandemic were not associated with higher stage (breast: odds ratio [OR] 1.071, 95% confidence interval [CI] 0.826–1.388; colorectal: OR 1.201, 95% CI 0.869–1.661; endometrium: OR 0.792, 95% CI 0.495–1.252; prostate: OR 1.171, 95% CI 0.765–1.794; and lung: OR 0.826, 95% CI 0.535–1.262). Interpretation: Cancer cases staged during the first year of the COVID-19 pandemic were not associated with higher stage; this likely reflects the prioritization of cancer procedures during times of reduced capacity. The impact of the pandemic period on staging procedures varied between cancer sites, which may reflect differences in clinical presentation, detection and treatment.

  Link(s) to publication:

  http://dx.doi.org/10.9778/cmajo.20220092

• Roseborough, A. D.; Saad, L.; Goodman, M.; Cipriano, L. E.; Hachinski, V. C.; Whitehead, S. N., 2023, "White matter hyperintensities and longitudinal cognitive decline in cognitively normal populations and across diagnostic categories: A meta‐analysis, systematic review, and recommendations for future study harmonization", Alzheimers & Dementia, January 19(1): 194 - 207.
  Abstract: Introduction: The primary aim of this paper is to improve the clinical interpretation of white matter hyperintensities (WMHs) and provide an overarching summary of methodological approaches, allowing researchers to design future studies targeting current knowledge gaps. Methods: A meta-analysis and systematic review was performed investigating associations between baseline WMHs and longitudinal cognitive outcomes in cognitively normal populations, and populations with mild cognitive impairment (MCI), Alzheimer's disease (AD), and stroke. Results: Baseline WMHs increase the risk of cognitive impairment and dementia across diagnostic categories and most consistently in MCI and post-stroke populations. Apolipoprotein E (APOE) genotype and domain-specific cognitive changes relating to strategic anatomical locations, such as frontal WMH and executive decline, represent important considerations. Meta-analysis reliability was assessed using multiple methods of estimation, and results suggest that heterogeneity in study design and reporting remains a significant barrier. Discussion: Recommendations and future directions for study of WMHs are provided to improve cross-study comparison and translation of research into consistent clinical interpretation.

  Link(s) to publication:

  http://dx.doi.org/10.1002/alz.12642

• Vilches, T. N.; Abdollahi, E.; Cipriano, L. E.; Haworth-Brockman, M.; Keynan, Y.; Sheffield, H.; Langley, J. M.; Moghadas, S. M., 2022, "Impact of non-pharmaceutical interventions and vaccination on COVID-19 outbreaks in Nunavut, Canada: a Canadian Immunization Research Network (CIRN) study", Bmc Public Health, December 22(1): 1042 - 1042.
  Abstract: Background: Nunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks. Methods: We used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals. Results: We found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015—5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880—4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593—2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798—15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222—265) even in the absence of NPIs. Conclusions: NPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.

  Link(s) to publication:

  http://dx.doi.org/10.1186/s12889-022-13432-1

• Tarride, J-E.; Cheung, M.; Hanna, T. P.; Cipriano, L. E.; Regier, D. A.; Hey, S. P.; Chan, K. K. W.; Mittmann, N., 2022, "Platform, Basket, and Umbrella Trial Designs: Issues Around Health Technology Assessment of Novel Therapeutics", Canadian Journal of Health Technologies, July 2(7)
  Abstract: Advancements in genomic and precision medicine have changed the way oncology clinical trials are designed. Compared to the traditional single tumour-based trial, master protocols, which are often classified as basket, umbrella, or platform trials, conduct studies on multiple subgroups under a single overarching protocol. This paper summarizes the discussion held during CADTH’s second webinar, which examined issues around health technology assessment of evidence generated using these trial designs. In this workshop, several experts were invited to present on the clinical, health economic, patient value, and ethical aspects associated with these new study designs. The discussion section of this paper summarizes the major points raised by the presenters, as well as questions from the audience and answers from the presenters.

  Link(s) to publication:

  https://canjhealthtechnol.ca/index.php/cjht/article/view/nm0002

  http://dx.doi.org/10.51731/cjht.2022.385

• Avan, A.; Hachinski, V.; Aamodt, A. H.; Alessi, C.; Ali, S.; Alladi, S.; Andersen, R.; Anderson, K. K.; Avan, A.; Azarpazhooh, M. R., et al., 2022, "Brain health: Key to health, productivity, and well-being", Alzheimer's and Dementia, July 18(7): 1396 - 1407.
  Abstract: Brain health is essential for physical and mental health, social well-being, productivity, and creativity. Current neurological research focuses mainly on treating a diseased brain and preventing further deterioration rather than on developing and maintaining brain health. The pandemic has forced a shift toward virtual working environments that accelerated opportunities for transdisciplinary collaboration for fostering brain health among neurologists, psychiatrists, psychologists, neuro and socio-behavioral scientists, scholars in arts and humanities, policymakers, and citizens. This could shed light on the interconnectedness of physical, mental, environmental, and socioeconomic determinants of brain disease and health. We advocate making brain health the top priority worldwide, developing common measures and definitions to enhance research and policy, and finding the cause of the decline of incidence of stroke and dementia in some countries and then applying comprehensive customized cost-effective prevention solutions in actionable implementation units. Life cycle brain health offers the best single individual, communal, and global investment.

  Link(s) to publication:

  http://dx.doi.org/10.1002/alz.12478

• Cipriano, L. E.; Haddara, W. M. R.; Zaric, G. S.; Enns, E. A., 2021, "Impact of University Re-opening on Total Community COVID-19 Burden", PLOS ONE, August 16(8): e0255782 - e0255782.
  Abstract: Background: University students have higher average number of contacts than the general population. Students returning to university campuses may exacerbate COVID-19 dynamics in the surrounding community. Methods: We developed a dynamic transmission model of COVID-19 in a mid-sized city currently experiencing a low infection rate. We evaluated the impact of 20,000 university students arriving on September 1 in terms of cumulative COVID-19 infections, time to peak infections, and the timing and peak level of critical care occupancy. We also considered how these impacts might be mitigated through screening interventions targeted to students. Results: If arriving students reduce their contacts by 40% compared to pre-COVID levels, the total number of infections in the community increases by 115% (from 3,515 to 7,551), with 70% of the incremental infections occurring in the general population, and an incremental 19 COVID-19 deaths. Screening students every 5 days reduces the number of infections attributable to the student population by 42% and the total COVID-19 deaths by 8. One-time mass screening of students prevents fewer infections than 5-day screening, but is more efficient, requiring 196 tests needed to avert one infection instead of 237. Interpretation: University students are highly inter-connected with the surrounding off-campus community. Screening targeted at this population provides significant public health benefits to the community through averted infections, critical care admissions, and COVID-19 deaths.

  Link(s) to publication:

  http://dx.doi.org/10.1371/journal.pone.0255782

• Avan, A.; Amiri, A.; Mokhber, N.; Erfanian, M.; Cipriano, L. E.; Stranges, S.; Shojaeianbabaei, G.; Abootalebi, S.; Azarpazhooh, M. R., 2021, "Association of lewy bodies, hippocampal sclerosis and amyloid angiopathy with dementia in community-dwelling elderly: A systematic review and meta-analysis", Journal of Clinical Neuroscience, August 90: 124 - 131.
  Abstract: Introduction We measured the proportion of Lewy body pathology (LB), hippocampal sclerosis (HS), and cerebral amyloid angiopathy (CAA) among community-dwelling people with and without dementia. Methods We searched for community-based cohorts with postmortem brain autopsy until 1 January 2020. We calculated the summary risk difference and 95% confidence interval (95% CI) using a random-effects model in R. Results We found 12 articles, comprising 2197 demented and 2104 non-demented participants. LB, HS, CAA were prevalent lesions among community-dwelling elderly (15%, 10%, and 24%, respectively). These significantly increased the risk of dementia (LB: risk difference 38%, 95% CI 20–56%, HS: 34%, 24–44%, CAA: 19%, 3–34%). 20% of cases with neocortical LB, 17% with bilateral HS, and 42% with moderate/severe CAA pathology remained non-demented by death. Discussion LB or HS or CAA are common neuropathologies among community-dwelling elderly. Although these lesions independently are associated with dementia, many remain non-demented, by death.

  Link(s) to publication:

  http://dx.doi.org/10.1016/j.jocn.2021.05.044

• Vilches, T. N.; Nourbakhsh, S.; Zhang, K.; Juden-Kelly, L.; Cipriano, L. E.; Langley, J. M.; Sah, P.; Galvani, A. P.; Moghadas, S. M., 2021, "Multifaceted strategies for the Control of COVID-19 Outbreaks in Long-Term Care Facilities in Ontario, Canada", Preventive Medicine, July 148: 106564 - 106564.
  Abstract: Abstract The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3%–28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2–4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4%–96.3%) and 95.8% (95% CrI: 95.5%–96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

  Link(s) to publication:

  http://dx.doi.org/10.1016/j.ypmed.2021.106564

• Yarmol-Matusiak, E. A.; Cipriano, L. E.; Stranges, S., 2021, "A comparison of COVID-19 epidemiological indicators in Sweden, Norway, Denmark, and Finland", Scandinavian Journal of Public Health, February 49(1): 69 - 78.
  Abstract: Aims: To compare the early impact of COVID-19 infections and mortality from February to July 2020 across the Nordic nations of Sweden, Norway, Denmark, and Finland through available public data sources and conduct a descriptive analysis of the potential factors that drove different epidemiological outcomes, with a focus on Sweden’s response. Methods: COVID-19 cases, deaths, tests, case age distribution, and the difference between 2020 all-cause mortality and the average mortality of the previous 5 years were compared across nations. Patterns in cell phone mobility data, testing strategies, and seniors’ care home deaths were also compared. Data for each nation were based on publicly available sources as of July 31, 2020. Results: Compared with its Nordic peers, Sweden had a higher incidence rate across all ages, a higher COVID-19-related death rate only partially explained by population demographics, a higher death rate in seniors’ care, and higher all-cause mortality. Sweden had approximately half as much mobility change as its Nordic neighbours until April and followed similar rates as its neighbours from April to July. Denmark led its Nordic peers in testing rates, while Sweden had the highest cumulative test-positivity rate continuously from mid-March. Conclusions: COVID-19 pushed Sweden’s health system to its capacity, exposed systemic weaknesses in the seniors’ care system, and revealed challenges with implementing effective contact tracing and testing strategies while experiencing a high case burden. Looser government restrictions at the beginning of the outbreak are likely to have played a role in the impact of COVID-19 in Sweden. In an effort to improve epidemic control, Sweden has increased testing rates, implemented more restrictive prevention measures, and increased their intensive care unit bed capacity.

  Link(s) to publication:

  http://dx.doi.org/10.1177/1403494820980264

• Bansback, N. J.; Barbosa, C.; Barocas, J.; Bayoumi, A. M.; Behrends, C.; Chhatwal, J.; Cipriano, L. E.; Coffin, P.; Goldhaber-Fiebert, J. D.; Hoch, J., et al., 2021, "How simulation modeling can support the public health response to the opioid crisis in North America: Setting priorities and assessing value", International Journal of Drug Policy, February 88: 102726 - 102726.
• Formosa, E. A.; Grainger, L. A.; Roseborough, A. D.; Sereda, A. M.; Cipriano, L. E., 2020, "A Survey of Canadian, Student-Run Campus Emergency Medical Response Teams", The Journal of Collegiate Emergency Medical Services, December 3(2): 11 - 19.
• Fairley, M.; Cipriano, L. E.; Goldhaber-Fiebert, J. D., 2020, "Optimal Allocation of Research Funds under a Budget Constraint", Medical Decision Making, August 40(6): 797 - 814.
  Abstract: Purpose. Health economic evaluations that include the expected value of sample information support implementation decisions as well as decisions about further research. However, just as decision makers must consider portfolios of implementation spending, they must also identify the optimal portfolio of research investments. Methods. Under a fixed research budget, a decision maker determines which studies to fund; additional budget allocated to one study to increase the study sample size implies less budget available to collect information to reduce decision uncertainty in other implementation decisions. We employ a budget-constrained portfolio optimization framework in which the decisions are whether to invest in a study and at what sample size. The objective is to maximize the sum of the studies’ population expected net benefit of sampling (ENBS). We show how to determine the optimal research portfolio and study-specific levels of investment. We demonstrate our framework with a stylized example to illustrate solution features and a real-world application using 6 published cost-effectiveness analyses. Results. Among the studies selected for nonzero investment, the optimal sample size occurs at the point at which the marginal population ENBS divided by the marginal cost of additional sampling is the same for all studies. Compared with standard ENBS optimization without a research budget constraint, optimal budget-constrained sample sizes are typically smaller but allow more studies to be funded. Conclusions. The budget constraint for research studies directly implies that the optimal sample size for additional research is not the point at which the ENBS is maximized for individual studies. A portfolio optimization approach can yield higher total ENBS. Ultimately, there is a maximum willingness to pay for incremental information that determines optimal sample sizes.

  Link(s) to publication:

  http://dx.doi.org/10.1177/0272989X20944875

• Roseborough, A. D.; Langdon, K. D.; Hammond, R.; Cipriano, L. E.; Pasternak, S. H.; Whitehead, S. N.; Khan, A. R., 2020, "Post-mortem 7 Tesla MRI detection of white matter hyperintensities: A multidisciplinary voxel-wise comparison of imaging and histological correlates", NeuroImage: Clinical, July 27
  Abstract: White matter hyperintensities (WMH) occur in normal aging and across diagnostic categories of neurodegeneration. Ultra-high field imaging (UHF) MRI machines offer the potential to improve our understanding of WMH. Post-mortem imaging using UHF magnetic resonance imaging (MRI) is a useful way of assessing WMH, however, the responsiveness of UHF-MRI to pathological changes within the white matter has not been characterized. In this study we report post-mortem MRI sequences of white matter hyperintensities in normal aging, Alzheimer’s disease, and cerebrovascular disease. Seven Tesla post-mortem MRI reliably detected periventricular WMH using both FLAIR and T2 sequences and reflects underlying pathology of myelin and axon density despite prolonged fixation time. Co-registration of histological images to MRI allowed for direct voxel- wise comparison of imaging findings and pathological changes. Myelin content and cerebrovascular pathology were the most significant predictors of MRI white matter intensity as revealed by linear mixed models. Future work investigating the utility of UHF- MRI in studying cell-specific changes within WMH is required to better understand radio-pathologic correlations.

  Link(s) to publication:

  http://dx.doi.org/10.1016/j.nicl.2020.102340

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