Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence.

Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore. METHODS: Logistic regression and linear models tested associations between triallelic (L'S', based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N=11,815) in 2008-09 and during 2004-07 in 4196 Singaporeans. RESULTS: In US Whites, L' allele carriers had higher SBP (0.9 mm Hg, 95% CI=0.26-1.56) and greater odds (OR=1.23, 95% CI=1.10-1.38) of more severe hypertension than those with S'S' genotypes. In African Americans, L' carriers had lower mean SBP (-1.27mm Hg, 95% CI=-2.53 to -0.01) and lower odds (OR = 0.78, 95% CI=0.65-0.94) of more severe hypertension than those with the S'S' genotype. In African Americans, those with L'L' genotypes had lower DBP (-1.13mm Hg, 95% CI=-2.09 to -0.16) than S' carriers. In Native Americans, L' carriers had lower SBP (-6.05mm Hg, 95% CI=-9.59 to -2.51) and lower odds of hypertension (OR = 0.34, 95% CI=0.13-0.89) than those with the S'S' genotype. In Asian/Pacific Islanders those carrying the L' allele had lower DBP (-1.77mm Hg, 95% CI=-3.16 to -0.38) and lower odds of hypertension (OR = 0.68, 95% CI=0.48-0.96) than those with S'S'. In the Singapore sample S' carriers had higher SBP (3.02mm Hg, 95% CI=0.54-5.51) and DBP (1.90mm Hg, 95% CI=0.49-3.31) than those with the L'L' genotype. CONCLUSIONS: These findings suggest that Whites carrying the L' allele, African Americans and Native Americans with the S'S' genotype, and Asians carrying the S' allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures.

Factors associated with diabetes-related distress over time among patients with T2DM in a tertiary hospital in Singapore.

BACKGROUND: Persistent diabetes-related distress (DRD) is experienced by patients with Type 2 Diabetes Mellitus. Knowing factors associated with persistent DRD will aid clinicians in prioritising interventions efforts. METHODS: A total of 216 patients were recruited from a tertiary hospital in Singapore, an Asian city state, and followed for 1.5 years (2011-2014). Data was collected by self-completed questionnaires assessing DRD (measured by the Problem Areas in Diabetes score) and other psychosocial aspects such as social support, presenteeism, depression, health-related quality of life (HRQoL) and excessive daytime sleepiness (EDS) at three time points. Clinical data (body-mass-index and glycated haemoglobin) was obtained from medical records. Change score was calculated for each clinical and psychosocial variable to capture changes in these variables from baseline. Generalized Linear Model with Generalized Estimating Equation method was used to assess whether baseline and change scores in clinical and psychosocial are associated with DRD over time. RESULTS: Complete data was available for 73 patients, with mean age 44 (SD 12.5) years and 67% males. Persistent DRD was experienced by 21% of the patients. In the final model, baseline HRQoL (OR = 0.56, p < 0.05) and change score of EDS (OR = 1.22, p < 0.05) was significantly associated with DRD over time. CONCLUSIONS: EDS might be a surrogate marker for persistent DRD and should be explored in larger samples of population to confirm the findings from this study.

Association of anthropometric measures with SF-36v2 PCS and MCS in a multi-ethnic Asian population.

PURPOSE: Obesity adversely affects health-related quality of life (HRQoL). Most studies have used body mass index (BMI) to measure obesity. Other measures of obesity, such as waist circumference (WC) or waist-to-hip ratio (WHR), may be better predictors of cardiovascular disease and mortality. We, therefore, examined the associations between other anthropometric measures and HRQoL in a multi-ethnic Asian population. METHODS: In this follow-up study from four previous cross-sectional surveys, HRQoL was measured, at follow-up, using the Short-Form 36 version 2 (SF-36v2) questionnaire. Linear regression was used to assess the relationship between anthropometric measures [BMI, WC, waist residuals (WR) (generated by regressing WC on BMI), WHR, waist-to-height ratio (WHtR) and height (Ht)] and HRQoL. We compared the models' R2, Akaike's information criteria (AIC), and Schwarz Bayesian information criteria (BIC) from the different models. RESULTS: Among 4,981 subjects, 47.6% were men aged 50.6 ± 12.2 and women aged 49.3 ± 11.6 years. All gender-specific anthropometric measures were significantly correlated with BMI, except WR. After adjusting for known determinants of HRQoL, we found significant associations between BMI, WC and WHtR with SF-36v2 Physical Component Summary (PCS) scores in women but not men. In contrast, after adjusting for known determinants of HRQoL, WR and WHR were significantly associated with SF-36v2 Mental component summary (MCS) scores in men, but not women. R², AIC and BIC were similar for all anthropometric measures in the final model. CONCLUSIONS: The associations between measures of central obesity and HRQoL differed between men and women. In women, associations were seen with SF-36v2 PCS, but measures of central obesity did not have significant associations with HRQoL after controlling for BMI. In men, an association between WC and SF-36v2 MCS was statistically significant independent of BMI. These gender differences require further investigation.

The ARIC predictive model reliably predicted risk of type II diabetes in Asian populations.

BACKGROUND: Identification of high-risk individuals is crucial for effective implementation of type 2 diabetes mellitus prevention programs. Several studies have shown that multivariable predictive functions perform as well as the 2-hour post-challenge glucose in identifying these high-risk individuals. The performance of these functions in Asian populations, where the rise in prevalence of type 2 diabetes mellitus is expected to be the greatest in the next several decades, is relatively unknown. METHODS: Using data from three Asian populations in Singapore, we compared the performance of three multivariate predictive models in terms of their discriminatory power and calibration quality: the San Antonio Health Study model, Atherosclerosis Risk in Communities model and the Framingham model. RESULTS: The San Antonio Health Study and Atherosclerosis Risk in Communities models had better discriminative powers than using only fasting plasma glucose or the 2-hour post-challenge glucose. However, the Framingham model did not perform significantly better than fasting glucose or the 2-hour post-challenge glucose. All published models suffered from poor calibration. After recalibration, the Atherosclerosis Risk in Communities model achieved good calibration, the San Antonio Health Study model showed a significant lack of fit in females and the Framingham model showed a significant lack of fit in both females and males. CONCLUSIONS: We conclude that adoption of the ARIC model for Asian populations is feasible and highly recommended when local prospective data is unavailable.

An open source tool to compute measures of inpatient glycemic control: translating from healthcare analytics research to clinical quality improvement.

OBJECTIVES: The objective of this study is to facilitate monitoring of the quality of inpatient glycemic control by providing an open-source tool to compute glucometrics. To allay regulatory and privacy concerns, the tool is usable locally; no data are uploaded to the internet. MATERIALS AND METHODS: We extended code, initially developed for healthcare analytics research, to serve the clinical need for quality monitoring of diabetes. We built an application, with a graphical interface, which can be run locally without any internet connection. RESULTS: We verified that our code produced results identical to prior work in glucometrics. We extended the prior work by including additional metrics and by providing user customizability. The software has been used at an academic healthcare institution. CONCLUSION: We successfully translated code used for research methods into an open source, user-friendly tool which hospitals may use to expedite quality measure computation for the management of inpatients with diabetes.

Evaluating the effectiveness of a multi-faceted inpatient diabetes management program among hospitalised patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs. METHODS: We designed a multi-faceted intervention program with the aim of reducing inpatient hypoglycemia and hyperglycemia. This was implemented over seven phases between September 2013 to January 2016, and covered all the non-critical care wards in a tertiary hospital. The program represented a pragmatic approach that leveraged on existing resources and infrastructure within the hospital. We calculated glucometric outcomes in June to August 2016 and compared them with those in June to August 2013 to assess the overall effectiveness of the program. We used regression models with generalised estimating equations to adjust for potential confounders and account for correlations of repeated outcomes within patients and admissions. RESULTS: We observed significant reductions in patient-days affected by hypoglycemia (any glucose reading < 4 mmol/L: OR = 0.71, 95% CI: 0.61 to 0.83, p <  0.001), and hyperglycemia (any glucose reading > 14 mmol/L: OR = 0.84, 95% CI: 0.71 to 0.99, p = 0.041). Similar findings were observed for admission-level hypoglycemia and hyperglycemia. Further analyses suggested that these reductions started to occur four to 6 months post-implementation. CONCLUSIONS: Our program was associated with sustained improvements in clinically relevant outcomes. Our described intervention could be feasibly implemented by other secondary and tertiary care hospitals by leveraging on existing infrastructure and work force.

Effects of external counter-pulsation on endothelial function assessed by peripheral artery tonometry, levels of glycaemia and metabolic markers in individuals with type 2 diabetes mellitus.

BACKGROUND AND AIMS: External counter-pulsation (ECP) generates sheer stress thereby improving endothelial function and anginal symptoms in coronary artery disease. Endothelial dysfunction is also involved in the pathogenesis of T2DM. The aim of this pilot study was to investigate the use of ECP at different doses in improving endothelial function and glycaemic markers in T2DM. METHODS: This prospective study involved 46 subjects with T2DM randomly assigned to receive 35 sessions of ECP at different regimens (0.5 h versus 1 h) and duration (7 versus 12 weeks). Endothelial function was evaluated by reactive hyperaemia index (RHI) via peripheral arterial tonometry at the start, midpoint and end of study. Other secondary outcomes included fasting glucose, HOMA-IR, HbA1c, blood pressure, lipid profile, weight and vibration sense. RESULTS: There was no change in RHI across all 3 regimens of ECP individually or collectively at the end of the study (ΔRHI +0.01%, p = 0.458). Glycaemic markers also remained unchanged at endpoint. Subgroup analysis showed an improvement in RHI (ΔRHI +20.6%, p = 0.0178) in subjects with more severe endothelial dysfunction at baseline. CONCLUSION: ECP did not show a beneficial effect on endothelial function or glycemic control in this South-East Asian population with T2DM at any of the three regimens. This may partly be explained by less severe endothelial dysfunction and less insulin resistance in our population at baseline.

Feasibility of representing adherence to blood glucose monitoring through visualizations: A pilot survey study among healthcare workers.

BACKGROUND: Measuring adherence to processes is one of the established ways to quantify the quality of healthcare. Providing timely feedback to healthcare workers on the level of adherence can improve process measures. However, it is challenging to present data on adherence to repetitive time-sensitive tasks in a clear manner. OBJECTIVES: We used inpatient glucose monitoring as a test case to explore the feasibility of using visualizations to communicate adherence to repetitive scheduled tasks to healthcare workers. METHODS: We selected four candidate plots that represented distribution across time: histogram, probability density function plot (pdf plot), violin plot and cumulative density function plot (cdf plot). Doctors and nurses involved in inpatient diabetes care in a tertiary hospital were invited to complete a self-administered questionnaire that measured self-reported baseline knowledge, performance, and perception towards the visualizations. Performance was assessed by determining if a participant was able to correctly identify visualizations representing protocol adherence. We also assessed the perception of usability of these visualizations for monitoring protocol adherence. Binomial regression models were used to identify factors associated with overall performance and perception. Logistic regression models with generalized estimating equation were used to compare performance and perception between visualizations, and identify effect modifiers. RESULTS: A total of 57 doctors and nurses completed the questionnaire. Participants were most familiar with histogram (87.7%), followed by cdf plot (61.4%), pdf plot (40.4%), and violin plot (7%). However, the percentages of participants who identified non-adherence using these plots were generally lower, ranging from 29.8% to 40.4%. Participants' perception of usability ranged from 14% to 17.5% across these visualizations. More favorable perceptions were found among participants with baseline knowledge for two or more visualizations (adjusted odds ratio: 3.21; 95%CI: 1.29, 7.96; p-value: 0.012) and having identified two or more non-adherent visualizations (adjusted odds ratio: 4.23; 95%CI: 1.95, 9.16; p-value: < 0.001). CONCLUSIONS: Adherence to repetitive time-sensitive tasks can be presented in the form of visualizations. However, nurses' and doctors' knowledge and understanding of these visualizations are generally poor. This may influence their perception of usability of these plots. Therefore, these visualizations need to be implemented in tandem with training on their interpretation, to enhance the usefulness of these plots in motivating quality improvement.

Patient characteristics and patterns of drug use for sleep complaints in the United States: analysis of National Ambulatory Medical Survey data, 1997-2002.

OBJECTIVE: The aims of this work were to characterize ambulatory patients in the United States presenting with primary or secondary insomnia complaints and resultant diagnoses, and to describe the characteristics of patients treated with medications commonly used for sleep complaints. METHODS: Data from the National Ambulatory Medical Care Survey for the years 1997 through 2002 were analyzed. Data were stratified by patient characteristics, physician specialty, resulting diagnosis, and medications prescribed or provided. The unit of analysis was the individual patient visit; statistical comparisons were made using the chi(2) test for categorical variables and the Rao-Scott design-adjusted chi(2) test for comparisons of patient age groups. P<0.05 was the criterion for statistical significance. Cells containing < 30 observations were not included in the statistical analysis. RESULTS: The data included 147,945 patient visit records; rates of physician response to the survey ranged from 62.9% in 1999 to 70.4% in 2002. Based on this sample, it was projected that 30 million office visits involved insomnia complaints over the 6-year period from 1997 to 2002 throughout the United States. With a total of 4.9 billion physician visits projected for that time period, 0.6% of visits were insomnia related. Women were 1.5 times more likely to have insomnia-related visits (P<0.001). Overall, the greatest proportion of insomnia patients of both sexes was between the ages of 18 and 64 years (P<0.001). Sleep difficulties were most frequently attributed to organic disorders, depression and/or anxiety, and primary insomnia (55.8%, 27.3%, and 9.8%, respectively; P<0.001). The most frequently prescribed or recommended medications were zaleplon/zolpidem and trazodone (28.5% and 32.0%, respectively; P<0.001). Zaleplon and zolpidem were most frequently used for patients with organic diagnoses and those aged < or =65 years (33.2% and 29.8%; P<0.001). CONCLUSIONS: Demographics of patients with insomnia and their diagnoses from 1999 to 2002 remained stable, but the use of medications changed predictably as newer agents became available.

Validity of a Revised Short Form-12 Health Survey Version 2 in Different Ethnic Populations.

INTRODUCTION: The Short Form-12 version 2 (SF-12v2) is a shorter version of the Short Form-36 version 2 (SF-36v2) for assessing health-related quality of life. As the SF-12v2 could not be resolved into the physical- and mental-component summary score (PCS and MCS, respectively) in the general population of Singapore, this study aims to determine and validate the Singapore SF-12 version 2 (SG-12v2). MATERIALS AND METHODS: The SG- 12v2 was generated using the same methodology as the SF-12v2. Bootstrap analysis was used to determine if the SG-12v2 were significantly different from the SF-12v2. Content validity was assessed using percentage of variance (R²) of the Singapore version of SF-36v2 PCS and MCS explained by the SG-12v2 items. Agreement between the SF-36v2 and the SG-12v2 was assessed using Bland-Altman diagrams. Criterion validity was demonstrated if effect size differences between SF-36v2 and SG-12v2 were small (Cohen's criteria). Known-group validity of SG-12v2 was reported for participants with and without chronic diseases. RESULTS: Five items differed between the SG-12v2 and SF-12v2. Bootstrap analysis confirmed that SG-12v2 and SF-12v2 were significantly different. The SG12v2 explained 94% and 79% of the R² of the SF-36v2 PCS and MCS, respectively. Agreement was good and effect size differences were small (<0.3). Participants with chronic diseases reported lower SG-12v2 scores compared to participants without chronic diseases. CONCLUSION: The SG-12v2 offers advantage over the SF-12v2 for use in the general population of Singapore. The SG-12v2 is a valid measure and will be particularly useful for large population health surveys in Singapore.

Diabetes Health Profile-18 is Reliable, Valid and Sensitive in Singapore.

INTRODUCTION: The Diabetes Health Profile-18 (DHP-18) measures diabetes-related psychological well-being in patients with type 2 diabetes mellitus (T2DM). It includes 3 subscales: psychological distress (PD), barriers to activity and disinhibited eating. The psychometric properties of the DHP have not been evaluated in Asia. The aim of this study was to determine the psychometric properties of the DHP in multiethnic Singapore. MATERIALS AND METHODS: Patients between the ages of 18 to 65 diagnosed with diabetes (either type 1 or type 2) for at least 1 year were recruited from a diabetes outpatient clinic in a tertiary hospital. They completed a set of self-administered questionnaires including sociodemographic information and the DHP. Validity of the DHP was evaluated using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Reliability was assessed with internal consistency and sensitivity was determined by effect size, associated with detecting a statistically significant and clinically important difference between various patient subgroups. RESULTS: A total of 204 patients with mean age 45.4 (11.9) years, comprising 64% males and 50% Chinese, 27% Indian and 12% Malay were studied. In CFA, model fit was poor. Forced 3-factor EFA supported the original 3-factor structure of the DHP. Convergent and discriminant validity was demonstrated (100% scaling success). DHP was sensitive across majority of social demographic, clinical and social-functioning determinants (i.e., effect size >0.3). Cronbach's alpha exceeded 0.70 for all subscales. Ceiling effects were negligible but large floor effects were seen for the PD subscale (23%). CONCLUSION: The DHP is valid, reliable and sensitive for measuring well-being in Asian patients with T2DM.

Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c and retinopathy in a multiethnic Asian population.

CONTEXT: Hemoglobin A1c (HbA1c) ≥ 6.5% (47.5 mmol/mol) has recently been included as a criterion for the diagnosis of diabetes mellitus. It is unclear whether this criterion is appropriate in Asians. OBJECTIVE: To examine the relationship between HbA1c and diabetes-specific moderate retinopathy in Asian ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: Four independent population-based cross-sectional studies (2004-2011) in Singapore representing the three major Asian ethnic groups (n = 13 170 adults aged ≥ 25 y: Chinese, 5834; Malays, 3596; and Indians, 3740). MAIN OUTCOME: Moderate retinopathy was assessed from digital retinal photographs and defined as a level >43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve for detecting moderate retinopathy were compared across ethnic groups at different HbA1c cut-points. RESULTS: HbA1c levels were higher in Indians and Malays compared to Chinese (P < .001). The prevalence of moderate retinopathy below HbA1c <6.5% was <1% in all ethnic groups. At HbA1c ≥ 6.5%, the sensitivity for detecting moderate retinopathy was lower in Chinese subjects compared to Indians and Malays (75.8 vs 86.0 and 85.3%), but specificity (89.7 vs 71.9 and 76.3%) was higher; however, positive predictive value and negative predictive value were similar among Chinese, Indians, and Malays (10.5, 12.3, 12.4%; and 99.6, 99.1, 99.2%, respectively). The AUCs were similar across all three ethnic groups (0.861, 0.851, and 0.853). CONCLUSIONS: Our study supports the use of HbA1c for diagnosing diabetes in Asians. Despite some interethnic variation in the relationship of HbA1c and retinopathy, a cut-point of 6.5% performs reasonably well in the three major Asian ethnic groups.

Establishing the thematic framework for a diabetes-specific health-related quality of life item bank for use in an english-speaking asian population.

AIMS: To establish a thematic framework for a Diabetes Mellitus (DM)-specific health-related quality of life (HRQoL) item bank by identifying important HRQoL themes and content gaps in existing DM-specific HRQoL measures and determining whether Patient-Reported Outcomes Measurement Information System (PROMIS) item banks are useful as a starting point. METHODOLOGY: English-speaking Type 2 DM patients were recruited from an outpatient specialist clinic in Singapore. Thematic analysis was performed through open coding and axial coding. Items from four existing DM-specific measures and PROMIS Version 1.0 and 2.0 item banks were compared with identified themes and sub-themes. RESULTS: 42 patients participated (25 men and 17 women; 28 Chinese, 4 Malay, 8 Indians, 2 other ethnicities). Median age was 53.70 years (IQR45.82-56.97) and the median disease duration was 11.13 (SD9.77) years. 10 subthemes (neutral emotions, coping emotions, empowered to help others, support from family, spend more time with family, relationships, financial burden on family, improved relationship, social support and religion/spirituality) were not covered by existing DM-specific measures. PROMIS covered 5 of 6 themes, 15 of 30 subthemes and 19 of 35 codes identified. Emotional distress (frustration, fear and anxiety) was most frequently mentioned (200 times). CONCLUSIONS: We had developed a thematic framework for assessing DM-specific HRQoL in a multi-ethnic Asian population, identified new items that needed to be written and confirmed that PROMIS was a useful starting point. We hope that better understanding and measurement of HRQoL of Asian DM patients will translate to better quality of care for them.

The Short Form 36 English and Chinese versions were equivalent in a multiethnic Asian population.

OBJECTIVE: The primary aim of this article was to evaluate measurement equivalence of the English and Chinese versions of the Short Form 36 version 2 (SF-36v2) and Short Form 6D (SF-6D). STUDY DESIGN AND SETTING: In this cross-sectional study, health-related quality of life (HRQoL) was measured from 4,973 ethnic Chinese subjects using the SF-36v2 questionnaire. Measurement equivalence of domain and utility scores for the English- and Chinese-language SF-36v2 and SF-6D were assessed by examining the score differences between the two languages using linear regression models, with and without adjustment for known determinants of HRQoL. Equivalence was achieved if the 90% confidence interval (CI) of the differences in scores, due to language, fell within a predefined equivalence margin. RESULTS: Compared with English-speaking Chinese, Chinese-speaking Chinese were significantly older (47.6 vs. 55.5 years). All SF-36v2 domains were equivalent after adjusting for known HRQoL. SF-6D utility/items had the 90% CI either fully or partially overlap their predefined equivalence margin. CONCLUSION: The English- and Chinese-language versions of the SF-36v2 and SF-6D demonstrated equivalence.

Prevalence and control of hypercholesterolaemia as defined by NCEP-ATPIII guidelines and predictors of LDL-C goal attainment in a multi-ethnic Asian population.

INTRODUCTION: Few studies in Asia have assessed the burden of hypercholesterolaemia based on the global cardiovascular risk assessment. This study determines the burden of hypercholesterolaemia in an Asian population based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and examines predictors of low-density lipoprotein cholesterol (LDL-C) goal attainment. MATERIALS AND METHODS: Five thousand and eighty-three Chinese, Malays and Asian-Indians living in Singapore were assigned to coronary heart disease (CHD)-risk category based on the NCEP-ATPIII guidelines. Awareness, treatment and control of hypercholesterolaemia based on risk- specific LDL-C goal were determined, including the use of lipid-lowering therapy (LLT). Cox-regression models were used to identify predictors of LDL-C above goal among those who were aware and unaware of hypercholesterolaemia. RESULTS: One thousand five hundred and sixty-eight (30.8%) participants were aware of hypercholesterolaemia and 877 (17.3%) were newly diagnosed (unaware). For those who were aware, 39.3% participants received LLT. Among those with 2 risk factors, only 59.7% attained LDL-C goal. The majority of them were taking statin monotherapy, and the median dose of statins was similar across all CHD risk categories. Among participants with 2 risk factors and not receiving LLT, 34.1% would require LLT. Malays or Asian-Indians, higher CHD risk category, increasing body mass index (BMI), current smoking and lower education status were associated with higher risk of LDL-C above goal. Being on LLT reduced the risk of having LDL-C above goal. CONCLUSION: The burden of hypercholesterolaemia is high in this multi-ethnic population especially those in the higher CHD risk categories, and might be partly contributed by inadequate titration of statins therapy. Raising awareness of hypercholesterolaemia, appropriate LLT initiation and titration, weight management and smoking cessation may improve LDL-C goal attainment in this population.