Clinical Public Health - Published 44(2) June 2021.

In this issue, Bernard Choi and colleagues have presented their vision of clinical public health as an approach to address complex health issues in our health system. To help stimulate discussion, CIM invited commen-taries from two distinguished scientists to present their views on the concept. We hope this discussion will ultimately guide the direction public health will follow.

Estimating cardiovascular disease incidence from prevalence: a spreadsheet based model.

BACKGROUND: Disease incidence and prevalence are both core indicators of population health. Incidence is generally not as readily accessible as prevalence. Cohort studies and electronic health record systems are two major way to estimate disease incidence. The former is time-consuming and expensive; the latter is not available in most developing countries. Alternatively, mathematical models could be used to estimate disease incidence from prevalence. METHODS: We proposed and validated a method to estimate the age-standardized incidence of cardiovascular disease (CVD), with prevalence data from successive surveys and mortality data from empirical studies. Hallett's method designed for estimating HIV infections in Africa was modified to estimate the incidence of myocardial infarction (MI) in the U.S. population and incidence of heart disease in the Canadian population. RESULTS: Model-derived estimates were in close agreement with observed incidence from cohort studies and population surveillance systems. This method correctly captured the trend in incidence given sufficient waves of cross-sectional surveys. The estimated MI declining rate in the U.S. population was in accordance with the literature. This method was superior to closed cohort, in terms of the estimating trend of population cardiovascular disease incidence. CONCLUSION: It is possible to estimate CVD incidence accurately at the population level from cross-sectional prevalence data. This method has the potential to be used for age- and sex- specific incidence estimates, or to be expanded to other chronic conditions.

Prevalence and incidence of dementia among indigenous populations: a systematic review.

BACKGROUND: Indigenous populations may be at increased risk, compared with majority populations, for the development of dementia due to lower education levels and socio-economic status, higher rates of diabetes, hypertension, cardiovascular disease and alcohol abuse, an aging population structure, and poorer overall health. This is the first systematic review investigating the prevalence and incidence of dementia in indigenous populations worldwide. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE, Embase, and PsycInfo for relevant papers published up to April 2015. Studies were included if they reported prevalence or incidence, the disease typically occurred after the age of 45, the study population included indigenous people, and the study was conducted in the general population. RESULTS: Fifteen studies representing five countries (Canada, Australia, the USA, Guam, Brazil) met the inclusion criteria. Dementia prevalence ranged from 0.5% to 20%. Retrospective studies relying on medical records for diagnoses had much lower prevalence rates and a higher risk of bias than population-based prospective studies performing their own diagnoses with culturally appropriate cognitive assessment methods. CONCLUSIONS: The prevalence of dementia among indigenous populations appears to be higher than it is for non-indigenous populations. Despite a building body of evidence supporting the need for dementia research among indigenous populations, there is a paucity of epidemiological research, none of which is of high quality.

Prevalence and Characteristics Associated with Breastfeeding Initiation Among Canadian Inuit from the 2007-2008 Nunavut Inuit Child Health Survey.

We aimed to determine the prevalence of, and factors associated with, breastfeeding initiation in Canadian Inuit. We used data from the Nunavut Inuit Child Health Survey, a population-based, cross-sectional survey conducted in the Canadian territory of Nunavut. Inuit children aged 3-5 years in 2007 or 2008 were randomly selected for the survey. Select household, maternal, infant and community characteristics were collected from the child's primary caregiver and entered into logistic regression models as potential predictors of breastfeeding initiation. Analyses were repeated in a subgroup of caregiver reports from biological mothers. The reported prevalence of breastfeeding initiation was 67.6% (95% CI 62.4-72.8) overall and 85.1% (95% CI 80.2-90.1) in a subgroup of caregiver reports from biological mothers. Adjusted prevalence odds ratios (pOR) indicate the primary caregiver was an important determinant of breastfeeding (adopted parent vs. biological mother: pOR = 0.03, 95% CI 0.01-0.07; other vs. biological mother: pOR = 0.33, 95% CI 0.14-0.74). Maternal smoking during pregnancy and having access to a community birthing facility were also potentially important, but not statistically significant (p > 0.05). In conclusion, data from the Nunavut Inuit Child Health Survey indicate breastfeeding is initiated for more than two-thirds of children, but rates are below the national average and this may be one of several pathways to poor health outcomes documented in many Inuit communities. Considered in the particular context of birthing facilities utilization and postnatal care arrangements in Inuit communities, these results suggest that increasing breastfeeding initiation will require health interventions that effectively engage all types of primary caregivers.

Growth measures among preschool-age Inuit children living in Canada and Greenland.

AIM: The present study reports findings from a study of preschool-age Inuit children living in the Arctic regions of Canada and Greenland. METHODS: We compare stature and obesity measures using cutoffs from the Centers for Disease Control and the International Obesity Task Force references. The sample is comprised of 1121 Inuit children (554 boys and 567 girls) aged 3-5 years living in Nunavut (n=376) and Nunavik (n=87), Canada, in the capital city of Nuuk, Greenland (n=86), and in Greenland's remaining towns and villages (n=572). RESULTS: Greenland Inuit children were significantly taller than their Canadian counterparts, with greatest height and weight observed among children from Nuuk. Overall prevalence of stunting was low with the three cutoffs yielding similar values for height-for-age z-scores. Obesity prevalence was higher among Canadian Inuit children than their Greenland counterparts. CONCLUSIONS: Inuit children have stature values consistent with those of the Centers for Disease Control reference and low prevalence of stunting, though geographic variability in mean stature values between Canadian and Greenlandic samples likely reflects differences in both socioeconomic status and genetic admixture. Obesity prevalence is high among both Canadian and Greenland Inuit preschoolers, with children living in the city of Nuuk exhibiting lower obesity prevalence than children living in either Nunavut or Nunavik, Canada or Greenland's towns and villages. Varying obesity prevalence may reflect varying degrees of food security in remote locations as well as the influence of stature and sitting height which have not been well studied in young Inuit children.

Autophagy and apoptosis of recombinant Chinese hamster ovary cells during fed-batch culture: effect of nutrient supplementation.

Upon nutrient depletion during recombinant Chinese hamster ovary (rCHO) cell batch culture, cells are subjected to apoptosis, type I programmed cell death (PCD), and autophagy which can be type II PCD or a cell survival mechanism. To investigate the effect of nutrient supplementation on the two PCDs and protein production in rCHO cells, an antibody-producing rCHO cell line was cultivated in batch and fed-batch modes. The feed medium containing glucose, amino acids, and vitamins was determined through flask culture tests and used in bioreactor cultures. In the bioreactor cultures, the nutrient feedings extended the culture longevity and enhanced antibody production. In addition, cells in the fed-batch culture showed delayed onset of both apoptosis and autophagy, compared with those in the batch culture. The inhibition of apoptosis was demonstrated by a decreased amount of cleaved caspase-7 protein and less fragmentation of chromosomal DNA. Concurrently, reduced LC3 conversion, from LC3-I to LC3-II, was observed in cells that received the feeds. Cultivation with pharmacological autophagy inducer (rapamycin) or inhibitor (bafilomycin A1) indicated that autophagy is necessary for the cells to survive under nutrient depletion. Taken together, the delayed and relieved cell death by nutrient supplementation could improve antibody production.

Proteomic understanding of intracellular responses of recombinant Chinese hamster ovary cells cultivated in serum-free medium supplemented with hydrolysates.

In order to understand the intracellular responses in recombinant CHO (rCHO) cells producing antibody in serum-free medium (SFM) supplemented with optimized hydrolysates mixtures, yielding the highest specific growth rate (µ, SFM#S1) or the highest specific antibody productivity (q(Ab,) SFM#S2), differentially expressed proteins in rCHO cells are measured by two-dimensional gel electrophoresis combined with nano-LC-ESI-Q-TOF tandem MS. The comparative proteomic analysis with basal SFM without hydrolysates revealed that the addition of hydrolysate mixtures significantly altered the profiles of CHO proteome. In SFM#S1, the expression of metabolism-related proteins, cytoskeleton-associated proteins, and proliferation-related proteins was up-regulated. On the other hand, the expression of anti-proliferative proteins and pro-apoptotic protein was down-regulated. In SFM#S2, the expression of various chaperone proteins and proliferation-linked proteins was altered. 2D-Western blot analysis of differentially expressed proteins confirmed the proteomic results. Taken together, identification of differentially expressed proteins in CHO cells by a proteomic approach can provide insights into understanding the effect of hydrolysates on intracellular events and clues to find candidate genes for cell engineering to maximize the protein production in rCHO cells.

Hyperosmotic stress induces autophagy and apoptosis in recombinant Chinese hamster ovary cell culture.

During recombinant Chinese hamster ovary (rCHO) cell culture, various events, such as feeding with concentrated nutrient solutions or the addition of base to maintain an optimal pH, increase the osmolality of the medium. To determine the effect of hyperosmotic stress on two types of programmed cell death (PCD), apoptosis and autophagy, of rCHO cells, two rCHO cell lines, producing antibody and erythropoietin, were subjected to hyperosmotic stress resulting from NaCl addition (310-610 mOsm/kg). For both rCHO cell lines, hyperosmolality up to 610 mOsm/kg increased cleaved forms of PARP, caspase-3, caspase-7, and fragmentation of chromosomal DNA, confirming the previous observation that apoptosis was induced by hyperosmotic stress. Concurrently, hyperosmolality increased the level of accumulation of LC3-II, a widely used autophagic marker, which was determined by Western blot analysis and confocal microscopy. When glucose and glutamine concentrations were measured during the cultures, glucose and glutamine concentrations in the culture medium at various osmolalities (310-610 mOsm/kg) showed no significant differences. This result suggests that induction of PCD by hyperosmotic stress occurred independently of nutrient depletion. Taken together, autophagy as well as apoptosis was observed in rCHO cells subjected to hyperosmolality.

A new approach to health research in Canada's North.

Over the past four years, despite low resource allocations to the North, northern residents and community organizations have taken significant initiatives towards the development of health research. In this commentary, we present a model for the development of northern health research based on our experiences in establishing the Institute for Circumpolar Health Research (ICHR) in the Northwest Territories. It is hoped that the lessons we have learned will inform decision-makers and encourage them to make strategic investments to support further health research capacity and institutional development within the North. Factors that have enabled the development of a health research institute in the North include leadership, a vision for health research, and the engagement of key partners and stakeholders. Challenges arise in the development of appropriate governance and policy for health research. There is an urgency to target resources to support the development of policies and governance for health research in northern jurisdictions. Both academic and community-based research need to be strengthened.

Cancer among the circumpolar Inuit, 1989-2003. I. Background and methods.

OBJECTIVES: This is first of 2 papers on the Circumpolar Inuit Cancer Review, an international collaborative effort involving researchers and health officials from Alaska, Canada and Greenland. It covers the period 1989-2003, updating the last review (1969-1988) and together provides an overview of the trends and patterns of cancer among the Inuit in 3 countries and over a 35-year period. METHODS: Inuit cancer cases by age-sex group and anatomic site were obtained from the regional cancer registries. The sources of the age-sex distribution of various Inuit populations include the population registry (Greenland), and annual estimates and periodic censuses (Alaska and Canada). Incidence rates were age-standardization by the direct method to the standard world population of the International Agency for Research on Cancer. CONCLUSIONS: This project demonstrates the feasibility of international partnerships in cancer surveillance, and when these partnerships are extended to other diseases and health conditions, they can contribute to the development of a Circumpolar Health Observatory.

Cancer among the circumpolar Inuit, 1989-2003. II. Patterns and trends.

OBJECTIVES: This is the second of 2 papers reporting on the result of the Circumpolar Inuit Cancer Review, an international collaborative effort involving researchers and health officials from Alaska, Canada and Greenland. METHODS: Inuit cancer cases by age-sex group and anatomic site were obtained from the regional cancer registries. RESULTS: Cancer in general is increasing among Inuit, in all regions, and among both men and women. Inuit continue to be at extreme high risk, relative to non-Inuit and to comparisons of global populations, for the historically recognized so-called traditional cancers (such as cancer of the nasopharynx and salivary glands). Among the so-called modern cancers prevalent in developed societies, lung cancer is rapidly increasing in incidence (especially in Canada), such that the rate in both Inuit men and women is the highest in the world; other cancers, such as colorectal cancer, are also on the rise (especially in Alaska), while breast and prostate cancer remain low relative to the non-Inuit population. The decline in cervical cancer is a positive development; in the 3 regions, the rate in Greenland is the highest. CONCLUSIONS: Data such as these can form the basis of interventions directed towards known risk factors such as smoking, diet, obesity, viral and bacterial infections, and low screening prevalence. Cancer surveillance is a basic task of the public health system; in the Arctic, it is particularly important as Inuit continue to undergo further changes in their life-styles and social environments.

Proactive Strategies to Address Health Equity and Disparities: Recommendations from a Bi-National Symposium.

INTRODUCTION: Health inequities persist in Canada and the United States. Both countries show differential health status and health care quality by social characteristics, making zip or postal code a greater predictor of health than genetics. Many social determinants of health overlap in the same individuals or communities, exacerbating their vulnerability. Many of the contributing factors and problems are structural and evade simple solutions. METHODS: In March 2017 a binational Canada-US symposium was held in Washington DC involving 150 primary care thought leaders, including clinicians, researchers, patients, and policy makers to address transformation in integrated primary care. This commentary summarizes the session's principal insights and solutions of the session tackling health inequities at policy and delivery levels. DISCUSSION: The solution lies in intervening proactively to reduce disparities-developing risk-adjustment measures that integrate social factors; increasing the socioeconomic, racial, and ethnic diversity of health providers; teaching cultural humility; supporting community-oriented primary care; and integrating equity considerations into health system funding. We propose moving from retrospective analysis to proactive measures; from equality to equity; from needs-based to strength-based approaches; and from an individual to a population focus.

Policy versus practice: a community-based qualitative study of the realities of pharmacy services in Nunavut, Canada.

OBJECTIVES: Nunavut is an Arctic territory in Canada subject to many social, economic and health disparities in comparison to the rest of the nation. The territory is affected by health care provision challenges caused by small, geographically isolated communities where staffing shortages and weather related access barriers are common concerns. In addition to national universal healthcare, the majority of the inhabitants of Nunavut (~85 %) are Inuit beneficiaries of no-charge pharmaceuticals provided through federal and/or territorial budgetary allocations. This research examines how existing pharmaceutical administration and distribution policies and practices in Nunavut impact patient care. METHODS: This grounded theory research includes document analysis and semi-structured interviews conducted in 2013/14 with patients, health care providers, administrators and policy makers in several communities in Nunavut. Thirty five informants in total participated in the study. Interviews were audiotaped, transcribed and analyzed with qualitative data analysis software for internal consistency and emerging themes. RESULTS: Four distinct themes emerge from the research that have the potential to impact patient care and which may provide direction for future policy development: 1) tensions between national versus territorial financial responsibilities influence health provider decisions that may affect patient care, 2) significant human resources are utilized in Community Health Centres to perform distribution duties associated with retail pharmacy medications, 3) large quantities of unclaimed prescription medications are suggestive of significant financial losses, suboptimal patient care and low adherence rates, and 4) the absence of a clear policy and oversight for some controlled substances, such as narcotics, leaves communities at risk for potential illegal procurement or abuse. CONCLUSIONS: Addressing these issues in future policy development may result in system-wide economic benefits, improved patient care and adherence, and reduced risk to communities. The interview informants who participated in this research are best positioned to identify issues in need of attention and will benefit the most from policy development to address their concerns.

Bcl-x(L) overexpression delays the onset of autophagy and apoptosis in hyperosmotic recombinant Chinese hamster ovary cell cultures.

Hyperosmolality in recombinant Chinese hamster ovary (rCHO) cell cultures induces autophagy and apoptosis. To investigate the effect of Bcl-x(L) overexpression on autophagy and apoptosis in hyperosmotic rCHO cell cultures, an erythropoietin (EPO)-producing rCHO cell line with regulated Bcl-x(L) overexpression was subjected to hyperosmolality resulting from NaCl addition in a batch culture and nutrient supplementation in a fed-batch culture. In the batch culture, Bcl-x(L) overexpression suppressed apoptosis, as evidenced by a decreased amount of cleaved caspase-7 and PARP. Concurrently, Bcl-x(L) overexpression also delayed autophagy, as indicated by reduced LC3 conversion, from LC3-I to LC3-II. As a result, the cell viability and EPO production were improved by Bcl-x(L) overexpression. In the fed-batch culture, the simultaneous application of Bcl-x(L) overexpression and nutrient feeding increased the culture longevity and maximum EPO concentration. Taken together, Bcl-x(L) overexpression delayed autophagy and apoptosis in hyperosmotic rCHO cell cultures, resulting in increased EPO production.

Effect of constitutively active Ras overexpression on cell growth in recombinant Chinese hamster ovary cells.

Constitutively active Ras (CA-Ras) is known to enhance cell growth through the induction of various signaling cascades including the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/ERK signaling pathways, although the cellular response is highly dependent on the cell type. To evaluate the effect of CA-Ras overexpression on cell growth in recombinant Chinese hamster ovary (rCHO) cells, an erythropoietin (EPO)-producing rCHO cell line with regulated CA-Ras overexpression (EPO-off-CA-Ras) was established using the Tet-off system. The CA-Ras expression level in EPO-off-CA-Ras cells was tightly regulated by doxycycline addition. Although CA-Ras overexpression slightly increased the viable cell concentration during the late exponential phase, it did not increase the maximum viable cell concentration or specific growth rate to a significant degree. Unexpectedly, CA-Ras overexpression in rCHO cells led only to the enhancement in the activation of the MAPK/ERK signaling pathway and not the PI3K/Akt signaling pathway. Taken together, CA-Ras overexpression in rCHO cells did not significantly affect cell growth; it also had no critical impact on viable cell concentration or EPO production, possibly due to a failure to activate the PI3K/Akt signaling pathway.