|Year : 2020 | Volume
| Issue : 1 | Page : 3-15
Adult immunization in occupational settings: A consensus of Indian experts
Parvaiz A Koul1, Subramanium Swaminathan2, Thirumalai Rajgopal3, V Ramsubramanian4, Bobby Joseph5, Shrinivas Shanbhag6, Ashish Mishra7, Sidram K Raut8
1 Professor and Head, Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Senior Consultant, Infectious Diseases, Gleneagles Global Health City, Chennai, Tamil Nadu, India
3 Vice President, Global Medical and Occupational Health, Unilever, Mumbai, Maharashtra, India
4 Senior Consultant, Infectious Diseases and Tropical Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
5 Professor, Community Health; Head, Occupational Health Services, St. John's Medical College, Bangalore, Karnataka, India
6 Medical Advisor, Chairman's Office, Reliance Industries Limited, Mumbai, Maharashtra, India
7 Health Director – Europe, Middle East, Africa and India, Dow Chemical International Pvt. Ltd. and President, Indian Association of Occupational Health, Mumbai Branch, Maharashtra, India
8 Director, Noble Hospital; Head of Blood Bank, Corporate and Overseas Business and Clinical Research, Noble Hospital, Pune, Maharashtra and President, Indian Association of Occupational Health, India
|Date of Submission||07-Mar-2020|
|Date of Decision||12-Mar-2020|
|Date of Acceptance||14-Mar-2020|
|Date of Web Publication||18-Mar-2020|
Dr. Thirumalai Rajgopal
VP, Global Medical and Occupational Health, Unilever and Non- Executive Independent Director, Apollo Hospitals Enterprise, Mumbai
Source of Support: None, Conflict of Interest: None
There is an increasing focus on instituting wellness programs at the workplace among organizations in India. Such programs are aimed at improving employee health, which in turn, helps in reducing absenteeism, as well as in increasing work productivity and improving employee engagement. Of note, adult vaccination plays a significant role in ensuring the well-being of employees, as well as in keeping an organization profitable. The burden of vaccine-preventable diseases (VPDs) in adults is increasing in India, causing significant morbidity and disability. Moreover, adult immunization is an underpublicized concept in India. There is an urgent need to create awareness about adult immunization in India, particularly in occupational health settings—both at the employee and employer levels. In view of this, an expert meeting was held under the aegis of the Indian Association of Occupational Health (IAOH) to discuss key issues pertaining to the burden of VPDs in the working population in India and to formulate guidelines on adult vaccination in occupational health settings. This consensus guideline document may act as a guide for organizations across India to create awareness about adult vaccination and also to design workplace vaccination programs to promote better health among employees.
Keywords: Adult vaccination, occupational health, recommendations, vaccine-preventable disease, wellness programs
|How to cite this article:|
Koul PA, Swaminathan S, Rajgopal T, Ramsubramanian V, Joseph B, Shanbhag S, Mishra A, Raut SK. Adult immunization in occupational settings: A consensus of Indian experts. Indian J Occup Environ Med 2020;24:3-15
|How to cite this URL:|
Koul PA, Swaminathan S, Rajgopal T, Ramsubramanian V, Joseph B, Shanbhag S, Mishra A, Raut SK. Adult immunization in occupational settings: A consensus of Indian experts. Indian J Occup Environ Med [serial online] 2020 [cited 2020 May 27];24:3-15. Available from: http://www.ijoem.com/text.asp?2020/24/1/3/280954
| Introduction|| |
Human capital, a crucial determinant of economic growth, is recognized as the level of education and health in a population. The term “expected human capital” signifies the number of years an individual remains at their peak productivity at the workplace between the ages of 20 and 64. A recent survey ranked India 158 among 195 countries in terms of expected human capital and, unfortunately, the average Indian's peak productive period lasts only 7 years, which is less than half that of a Chinese worker (peak productive period = 20 years). Besides, India ranks below all other countries in the South Asian region in terms of functional health.
People Matters-Sanofi Pasteur conducted a study in 221 corporate institutions in India in 2019 to assess the challenges of workplace-wellness programs. The survey showed that the majority (62%) of organizations did not take any measures to tackle an outbreak of infectious diseases at the workplace. Furthermore, lack of employee awareness is one of the crucial factors that affect the success of a wellness program. A recent survey conducted in major corporate organizations in metro cities showed a lack of understanding of influenza vaccines among employees. Another survey revealed that only 45% of employees were aware of flu shots offered at the workplace, in contrast to 77% among employers (who had implemented such programs).
Work performance challenges related to modifiable health behaviors (e.g. inadequate/lack of physical activity, smoking, obesity, etc.) are highly prevalent, ultimately leading to a loss of productivity and, thereby, affecting the economic/financial status of the organization. All these modifiable health factors not only contribute to increased levels of sickness absence but also give rise to the phenomena called “absenteeism and presenteeism.” Absenteeism refers to the count of days absent from work, whereas presenteeism refers to reduced productivity while at work. A survey has shown that acute diseases such as influenza, diarrhea, malaria, and dengue, followed by lifestyle diseases such as stroke, cardiovascular diseases, diabetes, and mental disorders are primary contributors to workplace absenteeism. Furthermore, insurance data for the financial years 2014–2017 for India showed that influenza and pneumonia had the highest average claim amount paid for these financial years. This draws our attention toward the increasing burden of vaccine-preventable diseases (VPDs) in adults in India. Moreover, VPDs have been found to be associated with significant morbidity and disability in India.
| Burden and Impact of Vpds in Working Population and Role of Adult Immunization|| |
In India, it is challenging to estimate the actual burden of various diseases due to the scarcity of systematic epidemiological data. Of note, the most common pneumococcal diseases, that is, meningitis and pneumonia, are associated with high morbidity and mortality rates.
[Table 1] shows the prevalence/incidence of VPDs in India.,,,,,
|Table 1: Prevalence/incidence of vaccine.preventable diseases (VPDs) in India,,,,,|
Click here to view
Burden of VPDs in workplace
The burden of influenza in the workplace is reflected in terms of work absenteeism, reduced work effectiveness, and increased physician office visits and hospitalization. Research suggests that influenza-like infections are associated with significant mean annual attack rates of 5.3% in vaccinated and 26.2% in nonvaccinated working employees. Influenza causes almost a 50% mean reduction in the activity level/effectiveness at work. A study by Tsai et al. reported that the mean work-loss hours per influenza-like illnesses is 23.6 h, and the work-loss hours are even higher in cases of influenza-like illness episodes associated with hospitalization (47 h). Furthermore, exposure to workplace inhalational hazards substantially contributes to the development of multiple chronic respiratory diseases, including pneumonitis, causing an occupational burden of 19%. Welders and those exposed to metal fumes are known to be at an increased risk for pneumococcal pneumonia and invasive pneumococcal disease (IPD).
Burden of comorbidities with increasing age and their impact
The proportion of the elderly population is rapidly increasing, and aging is frequently accompanied by different comorbidities, chronic diseases, and increased susceptibility to infectious diseases., Influenza increases the risk of hospitalization and intensive care unit (ICU) admission by 3–6-fold and 4-fold, respectively, in diabetes patients., Also, the risk of myocardial infarction is nearly six times higher within the 1st week of laboratory-confirmed influenza diagnosis. The overall incidence rate per 100,000 population of adult pneumococcal disease is 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, and 93.7 in adults with chronic heart disease. The incidence rates are increased with advancing age in adults with comorbidities such as chronic lung disease, diabetes, etc. A study conducted among 173 immunocompetent elderly individuals with community-acquired pneumonia revealed that cardiopulmonary comorbidities account for 42% of pneumonia cases in this study population.
Challenges of adult immunization in India
Adult immunization is a highly neglected and underpublicized issue. Even among published guidelines from international organizations such as the World Health Organization (WHO), there is a dearth of a consensus regarding the optimal strategy for adult immunization, and most importantly, the issue of adult immunization in developing countries remains unaddressed. Lack of awareness among the general population, failure of health care providers (HCPs) to monitor patients' vaccination status, lack of specialized vaccination centers for adults, and lack of drive among policymakers to promote adult vaccination are key challenges to adult immunization in India.,,
Significance of adult vaccination and its benefits to an organization
Adults require vaccination for numerous reasons. One of the primary reasons is age-related immunosenescence, which reduces an individual's resistance to infections., Moreover, adults are frequently associated with chronic illnesses that increase susceptibility to infections., Interestingly, the proportion of adults who die of VPDs each year is 350-fold higher vs the corresponding figure for children. The inability of childhood vaccination to offer long-term benefits, as well as the changing disease epidemiology with the emergence and reemergence of certain diseases (tuberculosis, malaria), is why adult vaccination is important.,,
Outcomes of adult vaccinations to organizations
Workplace vaccination has several benefits for employers as well as employees. Workplace vaccination leads to reduced sick leaves and doctor visits and improved health and morale among employees. This reduces absenteeism, improves work productivity, and translates to financial benefits for the employer., For instance, influenza vaccination was associated with a 23% reduction in the absence rate and a 30% improvement in lost working days and related expenses. This also led to a cost-benefit ratio of 4.2, that is, a return of €4 at the cost of €1 due to curtailed absenteeism. The economic benefits of polysaccharide 23-valent (PPSV23) and/or conjugate pneumococcal vaccine 13-valent (PCV13) in adults, the elderly, and at-risk groups have been evaluated in many studies., A sequential pneumococcal vaccination with PCV13 first, followed by unconjugated PPSV23, was associated with potential savings of €115–€187 million for medical and nonmedical costs due to a substantial reduction in total IPD cases, as well as hospitalized all-cause nonbacteremic pneumonia (NBP) and outpatient NBP cases. A Spanish dynamic transmission model reported that the use of PCV13 for 5 years in a cohort of patients aged 65–69 years would avoid 10,360 cases of pneumococcal disease and 699 deaths, leading to an increase of 14,736 life-years. This may result in a corresponding cumulative saving of €3.8 million at a fixed price (€4.9 million at current prices) and would be an efficient intervention for the Spanish National Health System.
A highly important aspect of workplace adult vaccination is to extend the benefits/provision of adult vaccination to the family members of employees. Considering the highly contagious nature of the VPDs such as influenza, varicella, and pneumococcal infections (caused by Streptococcus pneumoniae), extending vaccination benefits to family members may reduce the rate of absenteeism among employees, owing to self-infection or family obligation.,,
Role of vaccination in reducing comorbidities
Influenza and pneumococcal vaccines have beneficial effects beyond the direct advantages of vaccines. Influenza vaccines have been reported to reduce the risk of heart attack by 19%–45%, which is equipotent or better than preventive treatments such as cholesterol-lowering drugs (reduce risk 25–30%) and lifestyle changes such as quitting smoking (reduces risk by 32–43%). The risk of all-cause mortality is 31% lower in influenza-vaccinated individuals with heart failure as compared with nonvaccinated patients. A meta-analysis has shown that influenza vaccines have a protective effect against major adverse cardiovascular disease events. Influenza vaccination also helps in reducing hospitalization by 54% in elderly patients with diabetes.
On the other hand, pneumococcal vaccines are known to reduce the risk of comorbidities. In a meta-analysis of eight observational studies, pneumococcal vaccination was associated with a significant reduction in the risk of the acute coronary syndrome in the older population (≥65 years old). Vaccination with PCV13 induces antibody responses to vaccine serotypes in patients (≥50 years old) with end-stage renal disease and on dialysis at 2 months postvaccination. In diabetes patients, pneumococcal vaccination confers a significant reduction in morbidity and mortality related to pneumococcal disease. The Research Society for the Study of Diabetes in India (RSSDI) 2018 recommends patient education on pneumococcal and influenza vaccine to all adult diabetes patients. The recommendation is to use PCV13 for adults ≥50 years followed by a dose of PPSV23 at least 1 year later (and at least 5 years after their previous PPSV23 dose), depending on the clinical judgment of the physician. Pneumococcal vaccination also decreases the risk of myocardial infarction and cerebrovascular events in the elderly. The conjugated pneumococcal vaccine has shown promising effects in terms of reducing the rate of antibiotic resistance by slowing the spread of resistant pneumococcal serotypes (19A) and also by averting disease occurrence. Therefore, the use of antibiotics can be avoided. Dual vaccination with the pneumococcal and influenza vaccines is effective in protecting elderly people with chronic illness from developing complications associated with respiratory, cardiovascular, and cerebrovascular diseases—thereby reducing hospitalization, coronary or intensive care admissions, and death.
Adult vaccination plays an important role in reducing the burden of VPDs, as well as in reducing workplace absenteeism, thus, improving productivity. Ultimately, it contributes to greater profits for the organization. Considering the necessity for increased awareness regarding the often-underestimated concept of adult vaccination in India, an expert meeting was held on 1 December 2019 under the aegis of the Indian Association of Occupational Health (IAOH) with the purpose of drawing attention to these issues and working toward developing guidelines on adult vaccination in occupational health settings. The scientific deliberations led to the formulation of consensus recommendations on adult vaccination in the context of occupational health settings in India.
| Adult Vaccination: Current Guidelines in India and Different Recommendations|| |
Unlike the Pediatrics Immunization Guidelines, several divergences exist from region to region regarding adult vaccination in India. The most popular guidelines in India for adult vaccination are the WHO guidelines, guidelines of the Geriatric Society of India, the Advisory Committee on Immunization Practices (ACIP) guidelines from the Centers for Disease Control and Prevention (CDC), Association of Physicians of India—Expert panel guidelines, Research Society for Study of Diabetes in India guidelines, Indian Society of Nephrology guidelines, and Indian Medical Association (IMA) guidelines.,,
The recommended vaccines for all healthy adults in India are as follows:,
- Influenza (>19 years onwards)
- Pneumococcal (>50 years)
- Pneumococcal conjugate vaccine 13-valent
- Pneumococcal polysaccharide vaccine 23-valent
- Human papillomavirus (15–45 years)
- Herpes zoster (>60 years)
- DPT (diphtheria, pertussis, and tetanus) (19 years onwards)
- MMR (measles, mumps, and rubella) (19–60 years old).
Pneumococcal disease: Burden, serogroups, and available vaccines
Asia is highly burdened with pneumonia patients, with India being the highest contributor with 43 million cases. In India, pneumonia and meningitis are the most common IPDs. Pneumonia accounts for 39% of the total IPD cases. Pneumococcal infection is associated with an increased risk of hospitalization due to heart diseases, as well as high in-hospital mortality. In India, IPD is associated with the highest case-fatality rate (28%) among adults aged >50 years. According to the 2017 Global Burden of Disease study, the reported incidence and mortality of pneumococcal infection increased by 26% and 33% among the 50–69 years and >70 years age groups, respectively. The most common serotypes isolated in India are 1, 3, 5, 19F, 8, 14, 23F, 4, 19A, and 6B. These serotypes account for 54.9% of IPD cases. A high nonsusceptibility to co-trimoxazole and the slow emergence of resistance to penicillin, tetracycline, and erythromycin has been reported. Vaccines are advocated by various Indian health care bodies/groups for older and younger adults with certain medical conditions.
There are two types of pneumococcal vaccine: unconjugated capsular polysaccharide antigens (PPSV 23) and capsular polysaccharides conjugated with a protein carrier (PCV13). [Table 2] highlights the detailed characteristics of both vaccines.,,,
Studies reveal that the initial PCV13 dose has the potential to enhance responses to a subsequent PPSV23 dose, compared with PCV13 alone. Pneumococcal conjugate vaccine 13 displays a more robust or greater immune response compared to PPSV23 in the majority of shared pneumococcal serotypes.
Based on the serotype covered by the conjugated form, that is, PCV13, and considering the seroprevalence in India, it is crucial to add PCV13 to ensure coverage for all prevalent serotypes in the country. Different professional societies in India, such as the Geriatric Society, the Indian Society of Nephrology, the Association of Physicians of India, the RSSDI, IMA, and Mass Gathering Advisory Board Consensus Recommendation 2016, have recommended the implementation of pneumococcal vaccination in adults.,,,,,
Various guidelines have advocated the use of pneumococcal vaccines sequentially for preventing disease occurrence among older adults. The chronological evolution of pneumococcal vaccine recommendations from global advocacy groups is detailed in [Table 3].,
|Table 3: Chronological evolution of pneumococcal vaccine recommendations,|
Click here to view
Influenza: Burden and available vaccines
Influenza viruses are highly unstable in nature and cause pandemics. [Figure 1] highlights the year-wise prevalence of influenza and mortality due to influenza. In 2017, the virus was unusually widespread in various parts of the country and caused three times higher mortality than in the pandemic year, that is, 2009.
The following prefilled syringes of influenza vaccines are available in India:
- Trivalent inactivated vaccine
- Quadrivalent inactivated
- Live, attenuated nasal spray (lyophilized)
A number of studies have shown the beneficial effects and safety of concomitant use of pneumococcal and influenza vaccines [Table 4]., Therefore, PCV13 and influenza vaccine (trivalent/quadrivalent) can be recommended concomitantly.
|Table 4: Concomitant use of pneumococcal and influenza vaccines,|
Click here to view
Hepatitis A and B: Burden and available vaccines
Viral hepatitis is a major healthcare problem in India. The health threat posed by hepatitis is comparable to three dreadful CDs—HIV/AIDS, malaria, and tuberculosis.
Hepatitis A virus (HAV) is accountable for 10–30% of acute hepatitis and 5–15% of acute liver failure cases. The prevalence of hepatitis B is estimated to be 2–7% based on the presence of surface antigen., India has around 50 million hepatitis B virus (HBV) carriers. Chronic HBV infections are responsible for 40–50% of hepatocellular carcinoma and 20–30% of cases of cirrhosis.
Vaccines available for immunization against HAV include inactivated vaccines such as single-antigen (HAV antigen) vaccines or combination vaccines containing both HAV and HBV antigens. For hepatitis B, recombinant DNA, inactivated subunit vaccine is available.
Measles, mumps, rubella (MMR): Burden and available vaccines
According to the WHO global report, there were 55,399 cases of measles and 1,066 cases of rubella in India in 2018. Mumps outbreaks occur more in densely populated places such as hostels, colleges, schools, military barracks, and poor socioeconomic settings. In a sailor training center in India, a total of 58 cases of mumps were reported in 3 months. A recent study conducted by health science students at Manipal University, India found the prevalence of serological susceptibility to rubella to be 16.6%.
The available vaccines in India are listed below:
- Measles only (M).
- Combination of:
- Measles and rubella (MR)
- Measles, mumps, and rubella (MMR)
- Measles, mumps, rubella, and varicella (MMRV).
Diphtheria, pertussis, and tetanus (DPT): Burden and available vaccines
Globally, the rising incidence of diphtheria in adults is a point of concern, with around 600,000 cases reported annually. Data on the incidence of adult pertussis in India are scarce but the incidence of adult pertussis is assumed to be high in states where childhood immunization coverage is adequate because the reduced natural circulation of pertussis leads to infrequent adolescent boosting. Tetanus poses a public health problem in several parts of the world, especially in tropical developing countries. In 2008, tetanus caused more than 61,000 deaths worldwide.
The available DPT vaccines in India are listed below:
- DTwP: Diphtheria, tetanus, and whole-cell pertussis vaccine, commonly known as a triple antigen.
- DTaP: Diphtheria, tetanus, and acellular pertussis vaccine.
- Tdap: Diphtheria, tetanus, and acellular pertussis vaccine (reduced antigen content).
- DT: Diphtheria and tetanus vaccine.
- Td: Diphtheria (reduced dose) and tetanus vaccine.
Varicella (Chickenpox): Burden and available vaccines
In India, >30% of individuals aged 15 years or above are susceptible to varicella-zoster virus (VZV) infection, and the seroprevalence of VZV increases with age. In older individuals, varicella is more severe and prolonged with mortality rates being 15–25 times higher than in children. Recently, an outbreak of 110 cases of varicella was reported at a large private university in Chennai.
Typhoid: Burden and available vaccines
In India, the incidence of typhoid is 120/100,000 population-years in adults older than 15 years. Increasing antibiotic resistance and widespread multidrug-resistant strains make the treatment of typhoid difficult and challenging.
The typhoid vaccines available in India are listed below:
- Vi-capsular polysaccharide vaccine
- Vi-polysaccharide conjugate vaccine conjugated with tetanus toxoid (TCV)
Rabies: Burden and available vaccines
Rabies is almost always fatal but preventable. One-third of global human deaths due to rabies in all age groups occur in India. A study reported the annual incidence of human rabies in India as 20,565 with the majority of patients being adult males.
In India, the following rabies vaccines are available:
- Human diploid cell vaccine (HDCV)
- Purified chick embryo cell vaccine (PCEC)
- Purified duck embryo vaccine (PDEV)
- Purified Vero-cell rabies vaccine (PVRV)
Human papillomavirus (HPV): Burden and available vaccines
More than 80% of sexually active women acquire genital human papillomavirus (HPV) by 50 years of age. About 6.6% of women are estimated to harbor cervical HPV infection. HPV serotypes 16 and 18 are responsible for nearly 76.7% of cervical cancer cases in India.
Two HPV vaccines (bivalent and quadrivalent vaccines) are commercially available. Bivalent vaccine (HPV2) protects against HPV types 16 and 18, whereas the quadrivalent one (HPV4) protects against four types of HPV (6, 11, 16, and 18).
Vaccination schedule for health care workers: Recommendations
Ensuring health and safety in the work environment is of paramount importance. The adoption of safe working practices together with immunization will significantly improve the protection of the individual worker against specific VPDs. The ACIP strongly recommends that all health care workers should be vaccinated against (or have documented immunity to) hepatitis B, influenza, MMR, and varicella [Table 5].,
Vaccination schedule during pregnancy: Recommendations
[Table 6] provides recommendations for various vaccines during preconception and pregnancy.
Vaccination for travel and mass gatherings: Recommendations
Several factors such as place of travel, staying conditions, and activities at the place of the visit are to be considered while choosing immunization for travelers. Hajj is one of the largest annual mass gatherings in the world. Meningococcal vaccine is compulsory for Hajj pilgrims. A high prevalence of respiratory tract infections (RTIs), including pneumonia, is evident in Hajj pilgrims. With Hajj pilgrims being highly susceptible to RTIs due to factors such as age, previous illnesses, intense crowding, and air pollution, the Preventive Vaccination for Pneumococcal Disease in Mass Gatherings (PREVENT) experts in Saudi Arabia advise the administration of the pneumococcal vaccine. Tables 7 present vaccination recommendations for Hajj pilgrims and Kumbh Mela attendees.,
| Vaccination Program at Workplace|| |
In India, there are no guidelines or practices for vaccination in the workplace. A vaccination program at the workplace must ideally involve managers and supervisors. For a vaccination program at the workplace, the following points are to be considered:
- It is very important to have clear objectives for the vaccination program.
- Subsequently, an execution team needs to be formed. The leadership team must be involved.
- A strong communication plan needs to be developed, focusing on how vaccination, as a wellness program, benefits employees.
- To create awareness about vaccination at the workplace, an organization must design employee-centric ways of communication, such as:
- Displaying posters in break rooms, cafeterias, and other high-visibility areas with the date and time details of the program
- Circulation of different article communications (e.g. e-mailers, intranet, newsletters, etc.)
- Business leaders may take initiatives in communicating the importance of vaccines to employees, to encourage mass participation.
- Social media may be engaged in creating awareness.
- A comfortable and convenient location and time for vaccination may ensure better participation.
A vaccination program at the workplace must ideally involve managers and supervisors. The leadership team must be involved. A comfortable and convenient location and time for vaccination may ensure better participation.
Hosting a vaccination program in company
Hosting a vaccination program within company premises is a great way to demonstrate a company's commitment to providing accessible health and wellness benefits. Extending vaccination to employees' families can be a significant step to ensure better participation [Figure 2].
Tables 8 provide a summary of recommendations by IAOH for working adults
| Conclusion and Future Directives|| |
VPDs cause a substantial health care burden in India and should be effectively controlled with vaccination, especially in the workplace. Apart from the direct benefits of vaccination such as productivity and reduction in absenteeism, it is important to highlight the spin-off benefits of vaccination in terms of reduction in cardiovascular comorbidities and hospitalization. Adult vaccination potentially enhances company/business profits. Awareness must be created about vaccination and vaccine recommendations must be circulated among all working professionals in any industry. Extending the benefits of adult vaccination to the family members of employees is pertinent for ensuring wider protection; thus, the risk of contagion can be further reduced. This will keep the family safe and healthy and reduce the rate of absenteeism.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]