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Table 4 Summary of studies, level of evidence, and quality for health outcomes from SLT by region

From: The health impact of smokeless tobacco products: a systematic review

Author Subjects/studies Outcomes Impact on health outcome Level of evidence* Quality rating
Global
Mortality     
 Gupta [10] 14 studies IHD Mortality, stroke Fatal stroke: OR = 1.27; 95% CI 1.15–1.39 3A Poor
 Siddiqi [13] 32 studies DALYs and mortality 1.7 million, DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus 3A Poor
 Sinha [12] 16 studies Mortality due to all cause, cancer mortality All-cause mortality: OR = 1.33; 95% CI 1.11–1.34
All cancer mortality: OR = 1.31; 95% CI 1.16–1.47
IHD mortality: OR = 1.10; 95% CI 1.04–1.17
Stroke mortality: OR = 1.37; 95% CI 1.24–1.51
3A Poor
 Vidyasagaran [11] 19 studies IHD mortality, stroke mortality IHD deaths: OR = 1.15; 95% CI 1.01–1.30
Stroke deaths: OR = 1.39; 95% CI 1.29–1.49
3A Good
Morbidity
Cancer
 Asthana [52] 37 studies Oral cancer Oral cancer: OR = 3.52; 95% CI 2.75–4.51 3A Poor
 Siddiqi [13] 32 studies Oral, pharyngeal, esophageal cancers Mouth cancers: OR = 3.43; 95% CI 2.26–5.19
Pharynx cancer: OR = 2.23; 95% CI 1.55–3.20
Esophageal cancers: OR = 2.17; 95% CI 1.70–2.78
3A Poor
Cardiovascular
 Gupta [10] 14 studies IHD Mortality, stroke Stroke: OR = 1.18; 95% CI 1.04–1.32
Fatal stroke: OR = 1.27; 95% CI 1.15–1.39
Nonfatal stroke: OR = 1.03; 95% CI 0.91–1.14
3A Poor
 Gupta [9] 20 studies CHD CHD: OR = 1.05; 95% CI 0.96–1.15 2A Good
 Vidyasagaran [11] 19 studies IHD IHD: OR = 1.14; 95% CI 0.92–1.42
Stroke: OR = 1.01; 95% CI 0.90–1.13
3A Good
AMEA
Mortality
 Etemadi [14] 50,045 Overall mortality, IHD mortality, CVA mortality, cancer mortality Mortality: HR = 1.16; 95% CI 1.01–1.34
Cancer mortality: HR = 1.40; 95% CI 1.01–1.95
IHD mortality: HR = 1.32; 95% CI 1.05–1.67
CVA mortality: HR = 1.06; 95% CI 0.74–1.53
Respiratory mortality: HR = 1.73; 95% CI 0.94–3.19
2B Fair
 Gupta [10] 14 studies IHD mortality, stroke Fatal stroke: OR = 1.35; 95% CI 1.18–1.51 3A Poor
 Sinha [12] 16 studies Mortality, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke All-cause mortality: OR = 1.25; 95% CI 1.08–1.44
All cancer mortality: OR = 1.46; 95% CI 1.26–1.68
Stroke mortality: OR = 1.37; 95% CI 1.14–1.64
3A Poor
 Vidyasagaran [11] 19 studies IHD IHD mortality: OR = 1.05; 95% CI .076–1.47 3A Good
 Gajalakshmi [15] 22,460 cases, 429,306 controls All-cause mortality, cancer deaths, respiratory deaths, stroke deaths (verbal autopsy) All-cause mortality: RR = 1.3; 95% CI 1.2–1.4
Respiratory diseases combined: RR = 1.5; 95% CI 1.4–1.7
Respiratory tuberculosis: RR = 1.7; 95% CI 1.5–1.9
Cancers (all sites combined): RR = 1.5; 95% CI 1.4–1.7
Stroke: RR = 1.4; 95% CI 1.2–1.6
3B Poor
Morbidity
Cancer
 Gholap [34] Ecological analysis Head and neck cancer (r = 0.53) oropharynx cancer incidence 2C Fair
 Nair [32] 747 Squamous cell carcinoma No HR/OR reported 2C Poor
 Asthana [52] 37 studies Oral cancer Oral cancer in Southeast Asia: OR = 4.44; 95% CI 3.51–5.61
Oral cancer in Eastern Mediterranean:OR = 1.28; 95% CI 1.04–1.56
3A Poor
 Khan [20] 6 studies Squamous cell carcinoma Oral cancer: OR = 11.8; 95% CI 11.4–25.3; I2 = 67% 3A Good
 Prasad [78] 22 studies Six cancers Oral cancer: OR = 6.6 (95% CI 5.2–8.4)
Larynx: cancer OR = 1.42 (95% CI 0.69–2.90)
Lung cancer: OR = 2.15 (95% CI 1.22–3.78)
Esophagus cancer: OR = 3.46 (95% CI 1.95–5.72)
Oropharynx cancer: not significant
Hypopharynx cancer: not significant
3A Fair
 Quadri [22] 6 studies Oral cancer Oral cancer: OR = 38.74; 95% CI 19.50–76.96 3A Poor
 Siddiqi [13] 32 studies Oral, pharyngeal, oesophageal cancers Mouth cancers in India: OR = 5.12; 95% CI 3.27–8.02
Mount cancers in Pakistan: OR = 8.81; 95% CI 3.14–24.69
Pharynx cancer in India: OR = 2.60; 95% CI 1.76–3.85
Oesophageal cancers in India: OR = 2.57; 95% CI 2.20–3.00
Oesophageal cancers in Pakistan: OR = 8.20; 95% CI 1.45–27.47
3A Poor
Sinha [21] 25 studies Cancers Oral cancer: OR = 5.67; 95% CI 3.83–8.40
Pharyngeal cancer: OR = 2.69; 95% CI 2.28–3.17
Oesophageal cancer: OR = 3.17; 95% CI 2.76–3.63
3A Poor
 Alharbi [24] 70 cases, 140 controls Squamous cell carcinoma of oral cavity Shammah: OR = 33.01; 95% CI 3.22–39.88
Shisha: OR = 3.96; 95% CI 0.24–63
Shammah and shisha: OR = 35.03; 95% CI 11.50–65.66
3B Poor
 Awan [25] 134 cases, 134 controls Oral cancer Gutka: OR = 5.54; 95% CI 2.83–10.83; p < 0.001
Chewing tobacco: OR = 5.32; 95% CI 1.14–24.77; p = 0.033
3B Fair
 Chang [35] 549 cases, 601 controls Oral cavity, oropharynx, hypopharynx and larynx cancers Head and neck cancer: OR = 2.39; 95% CI 1.77–3.23 3B Fair
Gupta [26] 187 cases, 240 controls Squamous cell carcinoma OR = 8.51; 95% CI 4.90–14.77 3B Fair
 Hassanin [27] 196 Oral squamous cell carcinoma OR = 3.8; 95% CI 1.7–8.6 3B Poor
 Kadashetti [30] 100 cases, 100 controls Oral cancer OR = 2.8; 95% CI 1.2–7.0 3B Fair
 Khan [28] 84 cases, 174 controls Oral cancer OR = 21.0; 95% CI 6.1–72 3B Poor
 Khan [31] 90 cases, 120 controls Oral cavity cancer OR = 4.71; 95% CI 2.53–8.74 3B Poor
 Merchant [79] 79 cases, 143 controls Oral squamous cell carcinoma OR = 7.39; 95% CI 1.01–38.11 3B Fair
 Mohite [37] 217 cases, 217 controls Breast cancer OR = 2.35; 95% CI 1.01–5.51 3B Poor
 Nair [39] 100 cases, 200 controls Colorectal cancer OR = 1.53; 95% CI 0.58–4.0 3B Poor
 Quadri [23] 48 cases, 96 controls Oral cancer OR = 29.30; 95% CI 10.33–83.13 3B Fair
 Rajbongshi [36] 100 cases, 100 controls Breast cancer OR = 2.35; 95% CI 1.3–4.15 3B Poor
 Shah [38] 70 cases, 140 controls Gastric cancer OR = 4.37; 95% CI 1.92–9.95 3B Fair
 Sajad[80] 35 year-old male Squamous cell carcinoma OSCC in buccal mucosa and the reason for the same was exclusive unilateral tobacco chewing habit, with placement of the tobacco in the right mucobuccal fold 4 Fair
 Mahapatra [29] 134 cases, 268 controls oral cancer OR = 6.0; 95% CI 2.6–15.5 4 Poor
 Soni [33] 100 cases oral cancer Significant difference in oral cancer among patients who exclusively chewed tobacco than non-users of tobacco 4 Poor
Cardiovascular
 Gupta [9] 20 studies CHD CHD: OR = 1.02; 95% CI 0.86–1
Non-fatal CHD: OR = 1.10; 95% CI 1.00–1.20
Fatal CHD: OR = 1.03; 95% CI 0.86–1.19
2A Good
 Ahwal [19] 90 Hypertension, blood fasting blood glucose, diabetes, dyslipidemia Dyslipidemia: OR = 6.37; 95% CI 1.4–27.3
Hypertension: OR = 6.97; 95% CI 1.7–28.0
2C Poor
 Anand [17] 4038 Diabetes, asthma, hypertension Risk of diabetes and hypertension not statistically significant among self-reported exclusive SLT users compared to exclusive smokers 2C Fair
 Bhatt[81] 314 Systolic BP, diastolic BP Systolic hypertension associated with quantity of SLT use (B = 0.389 (SE = 0.131); p = 0.003), but diastolic hypertension was not (B = 0.122 (SE = 0.087); p = 0.160) 2C Good
 Mishra [18] 36 Latent CHD No difference in CHD between those who exclusively smoke and those who use exclusive SLT 2C Poor
 Gupta [10] 14 studies IHD Mortality, stroke Strok: OR = 1.35; 95% CI 1.18–1.51
Fatal stroke: OR = 1.35; 95% CI 1.18–1.51
3A Poor
 Vidyasagaran [11] 19 studies IHD IHD: OR = 1.40; 95% CI 1.01–1.95
IHD death: OR = 1.05; 95% CI .076–1.47
3A Good
 Behera [16] 423 stroke and MI Stroke: OR = 3.71; 95% CI 1.57–9.05
MI: OR = 2.34; 95% CI 1.10–5.40
4 Poor
Other
 Anand [17] 4038 Diabetes, asthma, hypertension, chronic lung disease Chronic lung disease: OR = 0.64; 95% CI 0.45–0.91 2C Fair
 Ahwal [19] 90 Hypertension, blood glucose, diabetes, dyslipidemia There was no difference in the prevalence of obesity (BMI >  = 25) among SLT users, smokers and non-tobacco users (p = 0.393) 2C Poor
 Mahapatra [29] 512 Oral health Gingival bleeding: OR = 1.710; 95% CI 1.2–2.43
Periodontal pockets: OR = 1.715; 95% CI 1.19–2.48
Loss of attachment: OR = 2.393; 95% CI 1.55–3.69
2C Fair
 Mathew [82] 800 Reproductive health Obstetrical problems: OR = 4.1; 95% CI 2.54–6.64
Neonatal problems: OR = 2.78; 95% CI 1.59–4.87
2C Poor
US
Mortality
 Fisher [41] 210,090 and 154,286 All-cause and disease-specific (cancer, cardiovascular) mortality Mortality (NHIS): HR = 1.03; 95% CI .83–1.29; (NLMS): HR = 0.82; 95% CI 0.59–1.13)
Malignant neoplasms of:
 Trachea, bronchus, and lung: HR = 2.98; 95% CI 0.91–9.76
 Digestive organs: HR = 1.01; 95% CI 0.32–3.20
 Esophagus: HR = 2.44; 95% CI .31–19.1
 Pancreas: HR = 1.36; 95% CI .19–9.98
 Ggenitourinary system: HR = 0.51; 95% CI 0.007–3.78
Heart disease (NLMS): HR = 1.07; 95% CI 0.65–1.75; (NHIS): HR = 1.20; 95% CI 0.91–1.58
Heart failure (NLMS): HR = 1.13; 95% CI 0.28–4.62; (NHIS): HR = 2.75; 95% CI 1.55–4.89
IHD (NLMS): HR = 0.95; 95% CI 0.49–1.83; (NHIS): HR = 1.06; 95% CI 0.75–1.49
2A Good
 Inoue-Choi [45] 65,335 Cancer-specific mortality Mortality: HR = 1.36; 95% CI 1.17–1.59
CHD mortality: HR = 1.63; 95% CI 1.27–2.09
Cancer mortality: HR = 1.48; 95% CI 1.04–2.12
Smoking-related cancer mortality: HR = 1.76; 95% CI 1.07–2.90
2B Good
 Rodu [43] 46,104 Mortality Younger (40–59 years)/all-cause mortality: HR = 1.44; 95% CI 1.12–1.84 2B Good
 Timberlake [44] 349,282 Mortality from all causes, all cancers, CHD, cerebrovascular disease and digestive system cancers All-cause mortality: HR = 1.01; 95% CI 0.93–1.10
All cancers: HR = 0.99; 95% CI 0.82–1.21
Cerebrovascular disease: HR = 0.92; 95% CI 0.67–1.27
Death from CHD: HR = 1.25; 95% CI 1.05–1.46
2B Fair
 Sinha [12] 16 studies Mortality due to all cause, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke All-cause mortality: OR = 1.17; 95% CI 1.12–1.22
All cancer mortality: OR = 1.14; 95% CI 1.01–1.29
Stroke mortality: OR = 1.44; 95% CI 1.30–1.59
IHD mortality: OR = 1.16; 95% CI 1.05–1.28
3A Poor
 Vidyasagaran [11] 19 studies IHD IHD death: OR = 1.03; 95% CI 0.83–1.27 3A Good
Morbidity
Cancer    
 Asthana [52] 37 studies Oral cancer OR = 4.72; 95% CI 0.66–33.62 3A Poor
 Siddiqi [13] 32 studies Oral, pharyngeal, oesophageal cancers Mouth cancers: OR = 0.95; 95% CI 0.7–1.2
Pharynx cancer: OR = 1.59; 95% CI 0.84–3.01
Oesophageal cancers: OR = 1.20; 95% CI 0.10–14.40
3A Poor
 Wyss [48] 6772 cases, 8375 controls oral, pharyngeal, and laryngeal cancers Head and neck cancer (HNC): OR = 1.71; 95% CI 1.08–2.70 3A Poor
Cardiovascular
 Gupta [9] 20 studies CHD OR = 1.04; 95% CI 0.83–1.24 2A Good
 Obisesan [47] 13,086 Hypertension Odds of hypertension: 0.88 times lower (95% CI 0.7907–0.9896) 2C Fair
 Gupta [10] 14 studies IHD Mortality, stroke Stroke: OR = 1.21; 95% CI 0.90–1.51
Fatal stroke: OR = 1.21; 95% CI 0.90–1.51
3A Poor
 Rostron [46] 24 studies IHD, stroke IHD: RR = 1.17; 95% CI 1.08–1.27
Stroke: RR = 1.28; 95% CI 1.01–1.62
3A Good
Other      
 Hernandez [41] 4930 Self-reported chronic health conditions At least one chronic health condition: OR = 1.49; 95% CI 1.23–1.81 2C Poor
 King [49] 2370 Self-reported depression, stress, mental health diagnosis Mental health diagnosis: AOR = 1.16; 95% CI 0.64–2.10; p = 0.594 Depression: AOR = 0.98; 95% CI 0.95–1.00
Stress: AOR = 1.03; 95% CI 1.00–1.05
2C Fair
Europe
Mortality
 Araghi [50] 417,872 All-cause mortality, colorectal cancer All-cause mortality: HR = 1.16; 95% CI 0.89, 1.50 2A Fair
 Wilson [51] 9582 Prostate cancer mortality, overall mortality Overall mortality: HR = 1.19; 95% CI 1.04–1.37
Prostate cancer-specific mortality: HR = 1.24; 95% CI 1.03–1.49
2B Fair
 Gupta [10] of 14 studies IHD Mortality, stroke Fatal stroke: OR = 1.30; 95% CI 0.96–1.63 3A Poor
 Sinha [12] 16 studies Mortality, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke IHD mortality: OR = 1.16; 95% CI 1.05–1.28 3A Poor
 Vidyasagaran [11] 19 studies IHD IHD death: OR = 1.38; 95% CI 1.13–1.67
Stroke death: OR = 1.28; 95% CI 0.98–1.68
3A Good
Morbidity
Cancer
 Araghi [50] 417,872 Colorectal cancer, all–cause mortality, cancer-specific mortality Colorectal cancer: HR = 1.22; 95% CI 0.91, 1.64
Colon cancer: HR = 1.02; 95% CI 0.81–1.29
Rectal cancer: HR = 1.29; 95% CI 1.02–1.30
2A Fair
 Araghi [53] 418,488 Pancreatic cancer HR = 0.96; 95% CI 0.83–1.11 2A Fair
 Asthana [52] 37 studies Oral cancer OR = 0.86; 95% CI 0.58–1.29 3A Poor
 Siddiqi [13] 32 Oral, pharyngeal, oesophageal cancers Mouth (oral cavity, tongue, and lip) cancers: Sweden: OR = 0.92; 95% CI 0.68–1.25; Norway: OR = 1.10; 95% CI 0.5–2.42
Pharynx cancer: Sweden: OR = 1.45; 95% CI 0.3–6.21
Oesophageal cancers: Norway: OR = 1.40; 95% CI 1.61–3.21; Sweden: OR = 1.26; 95% CI 1.02–1.56
3A Poor
Cardiovascular
 Gupta [9] 20 studies CHD OR = 0.95; 95% CI 0.86–1.04 2A Good
 Gupta [10] 14 studies IHD Mortality, stroke Stroke: OR = 1.04; 95% CI 0.94–1.15
Fatal stroke: OR = 1.30; 95% CI CHD-1.63
3A Poor
 Rostron [46] 24 studies IHD, stroke IHD: RR = 1.04; 95% CI 0.93–1.16
Stroke: RR = 1.04; 95% CI 0.92–1.17
3A Good
 Vidyasagaran [11] 19 studies IHD IHD: OR = 0.91; 95% CI 0.83–1.01
Stroke: OR = 1.01; 95% CI .90–1.13
3A Good
Other     
 Rauwolf [83] 347 Alcohol dependence No significant differences between the four groups regarding total abstinence (i.e. no alcohol consumption after end of treatment), days of alcohol consumption the last 30 days or grams of pure alcohol per week 2B Fair
 Yang [54] 348,601 Parkinson’s 60% lower Parkinson’s disease risk/HR = 0.41; 95% CI 0.28–0.61 2A Good
 Gudnadóttir [55] 16,082 Asthma, respiratory symptoms, sleep-related problems Asthma: OR = 1.49; 95% CI 1.20–1.85
Chronic bronchitis: OR = 1.47; 95% CI 1.21–1.78
Chronic rhinosinusitis: OR = 1.37; 95% CI 1.11–1.70
2C Good
  1. *Level of Evidence assigned using the Oxford Centre for Evidence Based Medicine framework [8]