Geographic variation and Factors associated with khat chewing among adult males 15-59 years in Ethiopia, EDHS 2016. Generalized Estimating Equation Approach

Background: Khat chewing has become prevalent in the world due to the improvement of road and air transportation. In Ethiopia, khat chewing is more prevalent and wildly practiced by men. Khat has a negative effect on social, economic and mental health. Therefore, this study aims to show spatial patterns and factors associated with khat chewing among male adults 15-59 years in Ethiopia. Methods : A total of 12,594 men who chew khat in their were included in this study. ArcGIS version 10.7 software was used to visualize spatial pattern chewing khat among adult men in Ethiopia. The Bernoulli model was applied using Kilduff SaTScan version 9.6 software to identify significant purely spatial clusters for chewing khat in Ethiopia. The robust standard error method of generalized estimating equations was used for the binary outcome variable from the clustered data and adjusted odds ratios with 95% confidence interval were reported. Results: A total of 12,594 participants were included in the analysis. The prevalence of ever khat chewing in this study was 3418 (27.14%) with 95% CI 26.37% to 27.92%. From EDHS 2016 survey the high proportion of chewing khat was located in Diredawa, Harari, Southern Oromia, Somai and Benishangu Gumuz Regions. In spatial scan statistics analysis, a total of 126 clusters (RR= 4.02, P-value < 0.001) was identified. Age group 30-44 (AOR=1.44, 95% CI: 1.27, 1.62), being single (AOR=1.86, 95% CI: 1.64, 2.12), Muslim religion (AOR=4.91, 95% CI: 3.69, 8.19), media exposure (AOR=0.77, 95% CI: 0.68, 0.86), working status(AOR=0.45, 95% CI: 0.39, 0.53), alcohol drinking (AOR=2.91, 95% CI: 2.43, 3.39) and region were statistically significant factors affecting chewing Khat in Ethiopia. Conclusions: The prevalence of chewing chat in Ethiopia was high and located in Diredawa, Harari, Southern Oromia, Somai and Benishangu Gumuz Regions. Older age group, single, drinker, media unexposed, had no work and Muslim religion follower should be given spatial attention in reducing the prevalence of chewing khat. Therefore, it is good to teach the health impact of khat chewing through media.

size and with independent selection in each sampling stratum. A household listing operation was implemented in the selected EAs, and the resulting lists of households served as the sampling frame for the selection of households in the second stage.

Study variables
Respondents ever chat chewing status, the outcome variable in this study was defined as a person who ever chewed khat in his lifetime. The independent variables were grossly classified into sociodemographic and economic factors: age, religion, marital status, educational status, place of residence, region, and Behavioral factors: alcohol drinking, source of information: reading newspaper, reading magazines, and watching television. Wealth ranking was grossly categorized into 5 major quintiles based on household assets as lowest (poorest), second (poorer), middle (middle), fourth (richer), and highest (richest) we recategorized in to three poor (poorest + poor), middle and rich (richest + rich) for ease of analysis.

Operational Definition
Ever chat chewer: Was defined as a respondent whoever chewed chat during his lifetime.
Alcohol drinking: was defined as a respondent who drunk during one month preceding the survey at least once per month.

Data collection tool and procedure
Raw data collected from all parts of the country on Men's whose age between 15-59 were extracted from 2016 EDHS by properly trained data collectors using standardized, structured, and pre-tested questionnaires. Initially, before the start of fieldwork, questionnaires were pretested Spatial Analysis

Spatial distribution of Khat chewing in Ethiopia
Among a total of 643 clusters, 621 were considered for the spatial analysis of khat chewing in Ethiopia( 21 clusters dropped because of no coordinate data in that cluster). Each point on the map represents one enumeration area with a prevalence of khat chewing in each cluster.

Spatial autocorrelation analysis
The spatial autocorrelation (Global Moran's I) statistic measures whether khat chewing patterns were dispersed, clustered or randomly distributed in the study area(1). Moran's I is a spatial statistics used to measure spatial autocorrelation by taking the entire data set and produce a single output value which ranges from -1 to +1. Moran's I Values close to −1 indicate disease dispersed, whereas I close to +1 indicate disease clustered and disease distributed randomly if I value is zero. A statistically significant Moran's I (p < 0.05) leads to rejection of the null hypothesis (khat chewing is randomly distributed) and indicates the presence of spatial autocorrelation

Incremental autocorrelation
Measures spatial autocorrelation for a series of distances and optionally creates a line graph of those distances and their corresponding z-scores. Z-scores reflect the intensity of spatial clustering, and statistically significant peak z-scores indicate distances where spatial processes promoting clustering are most pronounced. These peak distances are often appropriate values to use for tools with a Distance Band or Distance Radius parameter. This tool can help you select an appropriate Distance Threshold or Radius for tools that have these parameters, such as hot spot analysis(1).

Hot spot analysis (Getis-OrdGi* statistic)
Getis-OrdGi* statistics was computed to measure how spatial autocorrelation varies over the study location by calculating GI* statistic for each area. Z-score is computed to determine the statistical significance of clustering, and the p-value computed for the significance. Statistical output with high GI* indicates "hotspot" whereas low GI* means a "cold spot"

Spatial scan statistical analysis
A Bernoulli-based model was used in which events at particular places were analyzed if adults weather chewing chat or not coded as 1/0 variable. The scan statistics developed by Kulldorff and SaTScan™ software version 9.6 were used to identify the presence of purely spatial home deliver clusters. Scan statistics did scanning gradually across the space to identify the number of observed and expected observations inside the window at each location. The scanning window with the maximum likelihood was the most likely high performing clusters, and a p-value was assigned to this cluster.

Spatial interpolation:
The spatial interpolation technique is used to predict khat chewing for unsampled areas based on sampled EAs. For the prediction of unsampled EAs, we used deterministic and geostatistical Ordinary Kriging spatial interpolation technique using ArcGIS 10.7 software Data processing and Statistical analysis STATA version 14.1, excel and ArcGIS 10.1 were used for statistical and spatial analysis. Then data cleaning was carried out. Both descriptive and analytical studies were done after the data was weighted and presented on texts, tables, and graphs. Both bi-variable and multivariable analyses were performed to determine the existing association. Initially, bivariate analysis was performed and variables with a p-value of 0.2 and below were used for further analysis in the multivariable model. At the same time, Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR) with their corresponding confidence interval (CI) also determined for the bivariate and multivariate analysis, respectively.
Finally, a p-value less than 0.05 level of significance was used to declare the significance of association in the multi-variable model. The clustering effect was tested based on the region as a clustering variable. The robust standard error method of generalized estimating equations was used for the binary outcome variable from the clustered data.

Results
A total of 12,594 participants were included in the analysis. The prevalence of ever khat chewing in this study was 3418 (27.14%) with 95% CI 26.37% to 27.92%. Majority of them, 6426 (51.03%) of participants were in the age of 15-29 years. The majority of the participants 10098 (80.18%) were from rural and most of them 5876 (46.66%) were in the primary education class. The median age of the respondent was 29 with inter-quartile range (IQR) of 21-39. Around two-third of 7705(61.17 %), of participants, were married ( Table 1).

Spatial Distribution of Khat chewing
Among a total of 643 clusters, 621 were considered for the spatial analysis of khat chewing in Ethiopia( 21 clusters dropped because of no coordinate data in that cluster). Each point on the map represents one enumeration area with a prevalence of khat chewing in each cluster. The red color indicates areas with a high proportion of khat chewer whereas green color indicates EAs with a lower proportion of khat chewers. (Figure.2)

Spatial autocorrelation of Khat chewing
The spatial distribution of Khat chewing in Ethiopia was non-random in the EDHS 2016 survey. The global Moran's I value was 0.49 (P-value < 0.001) with z-score value 30.63 with that there is a less than 1% likelihood that this clustered pattern could be the result of chance (Figure3).

Incremental Spatial Autocorrelation Khat chewing
To determine spatial clustering for khat chewing, global spatial statistics were estimated using  (Figure 6 and Table 2). to 100% (Figure 7)

Factors affecting chewing Khat among adult male in Ethiopia
In the bivariate analysis, age group, sex, marital status, residence, religion, Educational status, region, wealth index, media exposure, working status, and alcohol drinking were associated factors with khat chewing at a p-value of less than or equal to 0.2. Consequently, these variables were subjected to multivariable analysis, and it was noted that age group, marital status, religion, region, media exposure, working status, and alcohol drinking were statistically significant variables associated with khat chewing at a p-value of 0.05 National Non-Communicable Disease STEPS the lifetime prevalence of khat chewing was (19%) (14) and in Dera woreda ever khat chewing was (19.9%) (18). In the former, the prevalence was the last 30 days duration of khat chewing whereas the current finding was a lifetime. For the second and the third studies, the difference might be nowadays the cultivation of khat is higher when compared within the previous time and in the current study only men were included but in the previous studies, both men and women were included.
The current finding was lower than the study finding of Somalis living in London the prevalence in the last one-week was 67% (11), in Saudi Arabia and Yemen, the prevalence of khat chewing was 36% (12) and 72%(9) respectively. In Yemeni men, the prevalence of khat chew was 90% (10). The discrepancy might be due to khat chewing is a deeply entrenched religious and socio-cultural tradition (6).
In this finding, different factors of khat chewing were assessed by the logistic regression model.
Individuals whose residency of Afar, Amhara, Oromia, Somali, Benishangul, SNNPR, Gambela, Harari, Addis Ababa, and Dire Dawa had higher odds of khat use when compared with Tigray. This study is in line with EDHS 2011 Ethiopia (13) the reason might be due to the fact that nowadays khat is cultivated throughout Ethiopia due to both socioeconomic and agroecological have contributed to khat farming expansions. The powerful force has perhaps been increased market prospects and prices of khat (26).
The odds of chewing khat among Ethiopian adults age group 30 to 44 and 45-59 increase by 44% and 25% respectively as compared to the age group 15-29 years. As the age increases, khat chewing behavior is increase which is supported by the 2011 EDHS data (13).
The odds of chewing khat among single individuals were about two times as compared to married.
This might be due to individuals who are single are high risk for substance use and unmarried individuals are positively associated with khat chewing (16). The odds of chewing Khat among Muslim religion followers were about five times higher as compared to Orthodox religion followers which are supported by the research done in EDHS, 2011 (13), Chiro town (19), Dera woreda (18) and Butajira (17). This could be due to the fact that khat use was acceptable in the socio-cultural and functional purposes with a restriction of the frequency, amount, and type of khat (27). Another reason might be to get maximum concentration level during praying, increase socialization, confirming norms and for stabilizing emotions (17) The odds of chewing khat decrease by 33% among media exposed adults as compared to their counterparts. This could be due to the fact that individuals who read magazines. newspapers, listen to the radio and watching television had the awareness of the bad consequence of khat use like; depression, anxiety, sleep disorder, conflict in the family, reduced appetite, neurological, and dental problems less likely to chew khat (21)(22)(23)(24).
The odds of khat chewing is increased by 91 % among alcohol drinkers when compared with a nondrinker. This is consistent with another finding; harmful drinking is common among khat users that account for 53.9% (28). The possible reason might be alcohol drinking is used to break the stimulating effect of khat therefore alcohol is helpful for sleep and used as self-treatment from khat induced distress (25).
The odds of khat chewing was decreased by 55% among individuals who have work when compared with counterparts. Perhaps, the jobless individuals spent their time with khat chewing.
This study has strengths of nationally representative data and advanced statistical models were used to account correlations within clusters. However, this study has limitations of the cross-sectional nature of the study may not indicate true causality. In addition, the effects of the health system and health worker factors were not assessed.

Conclusions
The prevalence of chewing khat in Ethiopia was higher when compared with other similar studies.
Men in older age groups, single, alcohol drinkers, Muslim religion follower, and work status should be given spatial attention in reducing the prevalence of chewing khat. Therefore, it is good to teach the health impact of khat chewing through media. Note; Others*= Catholic, cultural belief  Spatial interpolation of khat chewing among males in Ethiopia,EDHS 2016