Supreme Court of India additional affidavit 289 of 2016 Rotavirus vaccine trial data
SC 289 of 2016
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1. ADDITIONAL AFFIDAVIT ON BEHALF OF THE PETITIONER 1 20/-
2. ANNEXURE P1 TO P5 1 NIL
NEW DEHI: DATED: 20.07.2021
(PRASHANT BHUSHAN) COUNSEL FOR THE PETITIONERS 301, NEW LAWYERS CHAMBERS SUPREME COURT OF INDIA
NEW DELHI 110 001
CODE NO.: 515
DOL RAJ BHANDARI, REGD. CLERK, I.C. NO. 3745, MOBILE NO. 9868255076
IN THE SUPREME COURT OF INDIA
(CIVIL ORIGINAL JURISDICTION) WRIT PETITION (CIVIL) NO. 289 OF 2016
IN THE MATTER OF:
S. SRINIVASAN PETITIONER
VERSUS
UNIN OF INDIA & ORS. RESPONDENTS
PAPER BOOK
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COUNSEL FOR THE PETITIONER: PRASHANT BHUSHAN
INDEX
S. NO. PARTICULARS PAGES
1. Additional Affidavit on behalf of the Petitioner
2. Annexure P1: True copy of the Article published in New England Journal of Medicine dated 12.11.2020
3. Annexure P2: True copy of Reply to RTI dated 11.12.2020 issued by Translation health Science and technology Institute
4. Annexure P3: True copy of letter dated 29.12.2020 written by Dr. Puliyel to New England Journal of Medicine
5. Annexure P4: True copy of data issued by Dr. Puliyel to New England Journal of Medicine to 29.12.2020
6. Annexure P6: True copy of E-mail dated 20.05.2021 sent by New England Journal of Medicine to Dr. Puliyel
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ANNEXURE: P1
T he NEW ENGL A ND JOUR NA L of MEDICINE 8
Intussusception after Rotavirus Vaccine Introduction in India
S.N. Reddy, N.P. Nair, J.E. Tate, V. Thiyagarajan, S. Giri, I. Praharaj, V.R. Mohan,
S. Babji, M.D. Gupte, R. Arora, S. Bidari, S. Senthamizh, S. Mekala, K.B. Goru,
B. Reddy, P. Pamu, R.P. Gorthi, M. Badur, V. Mohan, S. Sathpathy, H. Mohanty,
M. Dash, N.K. Mohakud, R.K. Ray, P. Mohanty, G. Gathwala, S. Chawla, M. Gupta,
R. Gupta, S. Goyal, P. Sharma, M.A. Mathew, T.J.K. Jacob, B. Sundaram,
G.K.C. Purushothaman, P. Dorairaj, M. Jagannatham, K. Murugiah, H. Boopathy,
R. Maniam, R. Gurusamy, S. Kumaravel, A. Shenoy, H. Jain, J.K. Goswami,
A. Wakhlu, V. Gupta, G. Vinayagamurthy, U.D. Parashar, and G. Kang
The authors’ full names, academic de- grees, and affiliations are listed in the Appendix. Address reprint requests to Dr. Kang at the Division of Gastrointesti- nal Sciences, Christian Medical College Vellore, Ida Scudder Rd., Vellore, Tamil Nadu 632004, India, or at gkang@ cmcvellore.ac.in.
Drs. S.N. Reddy and Nair contributed equally to this article.
This is the New England Journal of Medi- cine version of record, which includes all Journal editing and enhancements. The Author Final Manuscript, which is the author’s version after external peer re- view and before publication in the Jour- nal, is available under a CC BY license at PMC7492078.
N Engl J Med 2020;383:1932-40. DOI: 10.1056/NEJMoa2002276
Copyright © 2020 Massachusetts Medical Society.
BACKGROUND
A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal im- munization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmar- keting surveillance data would be useful in assessing whether the risk of intus- susception would be similar to the risk seen with different rotavirus vaccines used in other countries.
METHODS
We conducted a multicenter, hospital-based, active surveillance study at 27 hospi- tals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was as- certained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case–control analysis was performed, with matching for age, sex, and location.
RESULTS
From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence,
0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case–control analysis.
CONCLUSIONS
The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Founda- tion and others.)
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INTUSSUSCEPTION AFTER ROTAVIRUS VACCINE IN INDIA 9
OSTLICENSURE STUDIES OF ROTAVIRUS vaccines have shown varying risks of intus- susception in different settings worldwide.
The association of intussusception with rotavi- rus vaccination was identified in 1998, when RotaShield (Wyeth–Lederle Vaccines), the first licensed rotavirus vaccine, was withdrawn be- cause of an increased risk of intussusception.1,2 Subsequent, large, prelicensure trials of the second-generation rotavirus vaccines Rotarix (GlaxoSmithKline Biologicals) and RotaTeq (Merck) did not show an increased risk of intussuscep- tion in clinical trials involving 65,000 to 70,000 infants.3,4 However, postmarketing surveillance of Rotarix in Australia, Brazil, England, Mexico, and the United States showed one to six excess cases of intussusception per 100,000 vaccinated children.5-10 Postmarketing surveillance of RotaTeq in Australia and the United States showed one to seven excess cases of intussusception per 100,000 vaccinated children.6,10
Despite the hypothesis that intussusception might be an adverse event associated with all rotavirus vaccines,11 the World Health Organiza- tion (WHO) recommended the introduction of rotavirus vaccine into childhood vaccination pro- grams because the projected incidences of rota- virus infection and deaths due to diarrhea that were averted were greater than the incidence of additional intussusception, resulting in a favor- able risk–benefit ratio.12 Recently, our under- standing of the safety of rotavirus vaccination in specific populations was further informed by the finding that in seven low-income African countries and South Africa, where vaccine effi- cacy has been lower than that in high-income countries, there was no increased risk of intus- susception after Rotarix vaccination.13,14
The vaccine we studied, Rotavac (Bharat Bio- tech International), is an oral monovalent, live, attenuated rotavirus vaccine that contains a naturally occurring bovine–human reassortant 116E strain (G9P[11]).15,16 The vaccine is admin- istered in a three-dose series at 6, 10, and 14 weeks of age, concurrent with other childhood vac- cines. It had an efficacy of 56% against severe rotavirus gastroenteritis in a multicenter, phase 3 clinical trial in India and was licensed in 2014.17 That trial, in which 6799 infants were randomly assigned in a 2:1 ratio to receive vaccine or pla- cebo, was not large enough to detect a small increased risk of intussusception.17 This vaccine was introduced into the Universal Immunization
Programme of India18 in 4 states in 2016, in 5 ad- ditional states in 2017, in 1 additional state in 2018, and in 10 additional states in 2019.19 More than 100 million doses of vaccine have been administered to Indian infants.
There are limited background data on intus- susception in India. Two studies have shown a general incidence of 18 intussusception cases per 100,000 infants and 20 cases per 100,000 infants.20,21 The Indian National Technical Advi- sory Group on Immunization and the WHO recommended the monitoring of vaccine safety after the introduction of the vaccine into the im- munization program22; in response to this recom- mendation, we established the Indian Intussus- ception Surveillance Network.23 Because the vaccine on which we now report has been prequalified by the WHO, safety data are important for India, for the Gavi Alliance, and for countries consider- ing the introduction of rotavirus vaccines.
STUDY SITES
Active surveillance for intussusception was con- ducted at 27 participating hospitals (Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org) that could carry out sentinel surveillance (called sentinel hospitals here) in 10 states in India in which half the population of India resides. Surveillance started in 4 states in April 2016 and was ex- panded concurrently with vaccine introduction. Detailed information about the methods is pro- vided in the protocol, which has been published previously23 and is available at NEJM.org.
All the infants who were younger than 2 years of age and who met level 1 diagnostic certainty for intussusception according to the Brighton Collaboration criteria were eligible for recruit- ment as study participants. Level 1 criteria of the Brighton Collaboration require the confirmation of intussusception by radiologic findings (spe- cifically, if the intussusception was reduced by pneumatic or hydrostatic methods or by contrast enema) or during surgery or at autopsy (Table S2).24 Surveillance staff completed paper case- report forms with information about patients’ sociodemographic and clinical characteristics, treatment, and outcomes and obtained copies of ultrasonographic images and reports and treat- ment notes. Information about rotavirus vaccina- tion status and a copy of the vaccination record
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T he NEW ENGL A ND JOUR NA L of MEDICINE 10
were obtained from the parents or guardians, and the dates of the first, second, and third vac- cinations were recorded. For children who were unvaccinated or partially vaccinated, we contacted the child’s health subcenter or primary health center to verify vaccination status.
We performed a matched case–control analy- sis that included a subgroup of patients with intussusception (case patients) and control in- fants, who were matched for age (date of birth within a window of ±30 days), sex, and location (same state of residence) and who had been ad- mitted with illness unrelated to the gastrointes- tinal tract within 30 days before or after the admission of the matched case patient. Copies of the vaccination card and vaccination informa- tion were obtained for control infants as they were for the case patients. All case-report forms were sent to the central data management team at Christian Medical College Vellore and entered into an audit trail–enabled SQL database, in which data cleaning and query resolution from sites were managed and validated against docu- ments for 10% of all the case-report forms.
STUDY OVERSIGHT
This study was approved by the institutional re- view board of Christian Medical College Vellore and by the institutional ethics committees of all the participating hospitals. Written informed con- sent was obtained from the parents or guardians of all enrolled infants and control participants.
Three authors designed the study, two au- thors led the data acquisition with all the inves- tigators and wrote the first draft of the manu- script, and four authors analyzed the data. The last author, who made the decision to submit the manuscript for publication, vouches for the ac- curacy of the data and for the fidelity of the study to the protocol.
STATISTICAL ANALYSIS
We calculated that 160 case patients would need to be enrolled25 for the study to have 80% power to detect a relative incidence of 2, within a 21-day risk window after the administration of any dose of vaccine, at a 5% level of significance; to detect a relative incidence of 2 after the first dose, the sample size was increased to 263 case patients.25 We used the self-controlled case-series method to assess the risk of intussusception after vac-
cine administration. We used conditional Pois- son regression analysis to calculate the relative incidence by comparing the incidence in the risk windows (i.e., 1 to 7 days, 8 to 21 days, and 1 to 21 days after each dose of vaccine) with the in- cidence in all other observational periods (non– risk periods) for each case patient, as required for self-controlled case-series analysis.23,26,27 We used the pseudolikelihood method27 to allow the contraindication of vaccination after an episode of intussusception, and event ascertainment was independent of vaccination status.
Considering the minimum and maximum ages at which rotavirus vaccine was administered, we restricted the analysis to children who were 28 to 365 days of age at the time of symptom onset. Children with a recurrent episode of intussus- ception were excluded from the study. Children with a verified vaccination history were included in the self-controlled case-series analysis, and children for whom vaccination history was based only on report from a parent or guardian or who had received a different rotavirus vaccine were excluded. Unvaccinated children were included in the analysis in order to adjust for the back- ground incidence of intussusception according to age. Age was controlled in the model with the use of 14-day windows. The confidence interval estimates were derived by means of bootstrap- ping with 1000 iterations.
For all the children, we attempted follow-up at approximately 18 months of age. During fol- low-up, data were obtained regarding the vital status of the child (alive or dead), the incidence of repeat intussusception, and the receipt of ad- ditional doses of rotavirus vaccine after the in- tussusception.
The matched case–control analysis involved a subgroup of infants with intussusception from the self-controlled case-series analysis for whom matched control participants were enrolled. Rota- virus vaccination status with confirmed vaccina- tion was needed for both the case patient and the matched control in order for the pair to be included. We used conditional logistic regres- sion to assess the ratio of the odds that case patients and controls who were matched for age, sex, and location were vaccinated during the same risk window. A reference date was created for controls, which was the date on which the control participant was the same age as the re-
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INTUSSUSCEPTION AFTER ROTAVIRUS VACCINE IN INDIA 11
spective case patient at the time of symptom onset. Exposure to the vaccine with the first, second, or third dose in the risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days before the reference date was determined. The matched odds ratios are reported as point estimates with 95% confidence intervals.
In sensitivity analyses for both the self-con- trolled case-series analysis and the matched case– control analysis, we used the date of admission instead of the date of symptom onset. All the statistical analyses were performed with the use of Stata software, version 13.1 (StataCorp).
CHARACTERISTICS AND CLINICAL FEATURES OF THE PATIENTS
A total of 970 children younger than 2 years of age with intussusception meeting the Brighton level 1 case definition were enrolled (Table S1). Of these, 258 children were excluded from the analysis because they were younger than 28 days of age or older than 365 days of age. Of the 712 children who were 28 to 365 days of age, 46 did not have a copy of the vaccination card and 40 had received a vaccine other than the one under study. Rotavirus vaccination status could not be verified by the health subcenter or primary health center for 37 children. Thus, 589 children with intussusception were included in the self- controlled case-series analysis (Fig. S1).
The median age of these 589 patients was 7 months (interquartile range, 5 to 9). Intussus- ception was more common among male infants than among female infants (ratio, 2:1). Blood in stools and vomiting were the most common symptoms (in 481 patients [82%] and 438 pa- tients [74%], respectively). Other than constipa- tion and blood in stools, there were no signifi- cant differences between vaccinated children and unvaccinated children. Ileocolic intussusception, which was seen in 498 children (85%), was the most common type of intussusception; ileoileal intussusception was observed in 33 children (6%). The treatment methods were hydrostatic or pneumatic reduction (in 200 children [34%]), surgical reduction (in 321 [54%]), and intestinal resection (in 68 [12%]). There were six deaths; the case fatality rate was 1%. (Details are pro- vided in Tables S3 and S4.)
VACCINE COVERAGE AND VACCINATION TIMING Among these 589 children, 289 (49%) had re- ceived all three doses of vaccine, 55 (9%) had received two doses, and 33 (6%) had received one dose; 212 children (36%) had not received any dose of vaccine. The median ages of the
patients at the administration of the first, sec- ond, and third doses were, respectively, 8 weeks (interquartile range, 7 to 9), 13 weeks (interquar-
tile range, 12 to 14), and 18 weeks (interquartile range, 16 to 20). Of the 377 children who had received the first dose of rotavirus vaccine, 330 (88%) had also received oral polio vaccine on the same day. Of the 344 and 289 children who had received the second and third doses of rotavirus vaccine, 300 (87%) and 240 (83%), respectively, had also received the second and third doses of oral polio vaccine on the same day. The third dose of vaccine is scheduled to be administered at 14 weeks of age, but children presented at a median age of 18 weeks, which overlapped with the peak age of intussusception (Fig. 1).
FOLLOW-UP IN THE SELF-CONTROLLED CASE-SERIES ANALYSIS
We were able to recontact 455 of the 589 chil- dren at a median age of 16 months (interquartile range, 13 to 22). Of those 455 children, 8 (2%) had a repeat episode of intussusception, and 7 (2%) died after hospital discharge. The deaths occurred between 4 months and 15 months after discharge; none of the deaths were due to intus- susception. Although further doses of the vac- cine are contraindicated after intussusception by the manufacturer, parents or guardians reported that 22 of 300 children (7%) who had not com- pleted their rotavirus immunization series had received at least one dose of rotavirus vaccine after intussusception (Table S5).
RISK OF INTUSSUSCEPTION AFTER VACCINATION
Self-Controlled Case-Series Analysis
After the first dose of vaccine, 2 cases of intus- susception occurred in the risk window of 1 to 7 days after receipt of the vaccine and 2 cases in the risk window of 8 to 21 days. After the sec- ond dose of vaccine, 4 cases of intussusception occurred in the risk window of 1 to 7 days and 15 cases in the risk window of 8 to 21 days. After the third dose of vaccine, 15 cases oc- curred in the risk window of 1 to 7 days and 22
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T he NEW ENGL A ND JOUR NA L of MEDICINE 12
cases in the risk window of 8 to 21 days (Fig. 2). The risk of intussusception in the 1-to-7-day window (relative incidence, 0.83; 95% confi- dence interval [CI], 0.00 to 3.00) and in the 8-to- 21-day window (relative incidence, 0.35; 95% CI,
0.00 to 1.09) after receipt of the first dose was not higher than the background risk. The risk of intussusception in the 1-to-7-day and 8-to-21-day windows after the second and third doses and the risk in the 1-to-21-day window after any dose were also not higher than the background risk (Table 1).
Matched Case–Control Analysis
The case–control analysis included 162 patients with intussusception who were matched for age, sex, and location with control participants who had a recorded vaccination history (Fig. S2). The odds of intussusception in the 1-to-7-day risk window (matched odds ratio, 1.00; 95% CI, 0.12 to 78.49) and in the 8-to-21-day risk window (matched odds ratio, 0.00; 95% CI, 0.00 to 1.51) after the first dose did not differ significantly among case patients and control participants. Similarly, the odds of intussusception in the 1-to-7-day and the 8-to-21-day windows after the second and third doses, or in the 1-to-21-day window after any dose, did not differ signifi-
cantly among case patients and control partici- pants (Table 2).
In analyses that used the date of admission instead of the date of symptom onset, the odds ratios did not differ significantly in all the risk windows in both the self-controlled case-series analysis and the matched case-control analysis (Tables S6 and S7). Similar risk estimates were also obtained with the self-controlled case-series analysis that was restricted to include only the 162 infants with intussusception who were in- cluded in the matched case–control analysis (Table S8).
DISCUSSION
An increased risk of intussusception was not detected in any risk window after the receipt of any dose of the rotavirus vaccine under study (Rotavac) among children in India in either the self-controlled case-series analysis or the case– control analysis. The results of our postmarket- ing, active surveillance study provide evidence that there was no adverse safety signal associ- ated with this vaccine in the Indian population. Our findings differ from those of postlicen- sure studies of Rotarix or RotaTeq in high-income and middle-income countries that showed a low-
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INTUSSUSCEPTION AFTER ROTAVIRUS VACCINE IN INDIA 13
level risk of intussusception after rotavirus vac- cination. Studies from Australia, England, Mexico, Singapore, and the United States showed an in- crease in the risk of intussusception by a factor of 2.6 to 8.4 in the 21 days after any dose of Rotarix vaccination.6-10,28 Studies from Australia and the United States have shown that RotaTeq vaccination was associated with an increase in the risk of intussusception by a factor of 2.6 to 9 in the 21 days after vaccination.6,10 Conversely, our findings appear to be similar to reports from sub-Saharan Africa and South Africa that did not show an increased risk of intussuscep- tion after the administration of a different rota- virus vaccine (Fig. 3).13,14
There are no defined criteria on which the risk of intussusception among individual children or in populations can be predicted, although the wide variation in background rates of intussus-
ception indicate that there may be population- based predictors.29 The earlier ages at which rota- virus vaccines are administered in low-income settings (at 6, 10, and 14 weeks), in contrast to the ages of vaccination in high-income countries (at 2, 4, and 6 months), may be one reason for this lack of association. In addition, the co- administration of rotavirus vaccine with oral polio- virus vaccine may decrease vaccine rotavirus replication in the intestinal epithelium,30 thus reducing the likelihood of triggering an intus- susception. In Brazil, no increased risk of intus- susception was found after the administration of the first dose of Rotarix vaccine, a situation in which the rotavirus vaccine was coadministered with oral polio vaccine.5 In our study, 88%, 87%, and 83% of the infants received the first, sec- ond, and third doses, respectively, of rotavirus vaccine and oral polio vaccine on the same day,
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T he NEW ENGL A ND JOUR NA L of MEDICINE 14
and no increased risk of intussusception was found after any dose.
The safety findings regarding the two dif- ferent rotavirus vaccines in Africa13,14 and India (the current study) are interesting in the con- text of reduced vaccine performance in these geographic settings. The immunogenicity and efficacy of oral vaccines, including rotavirus vaccines, are lower in low-resource communi- ties than in high-income countries.30,31 Factors, such as inhibition by higher levels of maternal antibodies in serum or breast milk and the coadministration of oral polio vaccine, that lower the effective titers of vaccine virus, thus reducing vaccine virus replication and hence immunogenicity, might also lower the risk of intussusception. Other factors, such as micro- nutrient deficiencies, malnutrition, environ- mental enteropathy, and early and constant
* Shown is the relative incidence of intussusception in the risk windows after the first, second, and third doses of Rotavac vaccine in 589 Indian infants who were 28 to 365 days of age and who had a confirmed history of having received or not received rotavirus vaccination. Relative incidence was calculated by the self-controlled case-series method. Of the 589 children included in the analy- sis, 377 (64%) had been vaccinated with one or more doses, and 212 (36%) had not received any dose of the rotavirus vaccine under study. The date of intussusception was defined as the date of symptom onset.
Table 2. Matched Odds of Intussusception in Risk Windows after Rotavirus Vaccination in Case–Control Pairs of Indian Infants.*
Dose and Risk Window No. of Cases No. of Controls Matched Odds Ratio (95% CI)
Dose 1
1–7 days 1 1 1.00 (0.12–78.49)
8–21 days 1 5 0.00 (0.00–1.51)
1–21 days 2 6 0.00 (0.00–1.51)
Dose 2
1–7 days 1 1 1.00 (0.01–78.49)
8–21 days 3 3 1.00 (0.07–13.79)
1–21 days 4 4 1.00 (0.13–7.46)
Dose 3
1–7 days 6 3 2.50 (0.41–26.25)
8–21 days 7 7 1.00 (0.26–3.74)
1–21 days 13 10 1.40 (0.49–4.42)
* Shown are the matched odds of intussusception in the risk windows after the first, second, and third doses of rotavirus vaccine in 162 case–control pairs of Indian infants. The infants were matched for age, sex, and location and had a confirmed rotavirus vaccination history with the vaccine under study. The date of intussusception onset was defined as the date of symptom onset.
exposure to other gut pathogens, are also pro- posed to affect mucosal and systemic respons- es to vaccination30-32 and could be responsible for the lower background and vaccine-associ- ated intussusception rates in low-resource set- tings.
Our large, active surveillance study of intus- susception, with high-quality countrywide data on intussusception and its management and con- sequences, including a case fatality rate, adds safety data to the literature on a relatively new vaccine that has been prequalified by the WHO. Death occurred in 1% of the Indian infants who were hospitalized with intussusception, whereas in a similar study in Africa, 12% of the children with intussusception died.13
Our study has certain limitations, which in- clude the exclusion of 12% of eligible infants who had inconclusive evidence of vaccination, an inability of the study to assess an association between intussusception and nutritional status, and a lack of estimates of community-based in- cidence and case fatality rates. However, back- ground rates of intussusception are not needed for a self-controlled case-series analysis because case patients act as their own control and were identified independent of their vaccination status. Given the large sample size, the study was ade- quately powered to detect small increases in risk in a 1-week or 3-week window after vaccination and showed none. A limitation of the case–con- trol analysis is the relatively smaller size, because
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INTUSSUSCEPTION AFTER ROTAVIRUS VACCINE IN INDIA 15
control participants were enrolled for only a subgroup of case patients, and the analysis was adjusted for sex but not for other potential con- founders. Nonetheless, the risk estimates from the self-controlled case-series analysis and the case–control analysis were similar except for the wider confidence intervals in the case–control analysis.
In this postmarketing, active surveillance study, we found that Rotavac, an oral rotavi- rus vaccine produced in India, was not associ- ated with intussusception in the population studied.
The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).
Supported by a grant (OPP1165083) from the Bill and Melinda Gates Foundation, through the Translational Health Science and Technology Institute and the CDC Foundation, with Chris- tian Medical College Vellore as a subawardee, and by a Fogarty International Center Global Infectious Disease Research Train- ing Grant (D43 TW0007392, to Dr. Kang).
No potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank all the participants and their parents and guardians and the surveillance staff at all the sentinel hospitals.
APPENDIX
The authors’ full names and academic degrees are as follows: Samarasimha N. Reddy, M.D., Nayana P. Nair, M.Sc., Jacqueline E. Tate, Ph.D., Varunkumar Thiyagarajan, M.Sc., Sidhartha Giri, M.D., Ph.D., Ira Praharaj, M.D., Ph.D., Venkata R. Mohan, M.D., Sudhir Babji, M.D., Mohan D. Gupte, M.D., Rashmi Arora, M.D., Sunita Bidari, D.N.B., Sowmiya Senthamizh, M.P.H., Suhasini Mekala, M.D., Krishna B. Goru, M.D., Bhaskar Reddy, M.Ch., Padmalatha Pamu, M.D., Rajendra P. Gorthi, M.Ch., Manohar Badur, M.D., Vittal Mohan, M.Ch., Saroj Sathpathy, M.D., Hiranya Mohanty, M.Ch., Mrutunjay Dash, M.D., Nirmal K. Mohakud, M.D., Rajib K. Ray, M.D., Prasantajyoti Mohanty, B.D.S., Geeta Gathwala, M.D., Suraj Chawla, M.D., Madhu Gupta, M.D., Ph.D., Rajkumar Gupta, M.D., Suresh Goyal, M.D., Pramod Sharma, M.D., Mannancheril A. Mathew, M.D., Tarun J.K. Jacob, M.Ch., Balasubramanian Sundaram, M.D., Girish K.C. Purushothaman, Ph.D., Priyadarishini Dorairaj, M.D., Muthukumaran Jagannatham, M.Ch., Kulandaivel Murugiah, M.D., Hemanthkumar Boopathy, M.Ch., Raghul Maniam, M.Ch., Rajamani Gurusamy, M.Ch., Sambandan Kumaravel, M.Ch., Ashwitha Shenoy, M.Ch., Hemant Jain, M.D., Jayanta K. Goswami, M.D., Ashish Wakhlu, M.Ch., Vineeta Gupta, M.D., Gopinath Vinayagamur- thy, M.Ch., Umesh D. Parashar, M.B., B.S., M.P.H., and Prof. Gagandeep Kang, M.D., Ph.D.
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INTUSSUSCEPTION AFTER ROTAVIRUS VACCINE IN INDIA 16
The authors’ affiliations are as follows: the Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences (S.N.R., N.P.N., V.T., S. Giri, I.P., S. Babji, S. Bidari, S. Senthamizh, G.K.), and the Department of Community Health (V.R.M.), Christian Medical College Vellore (T.J.K.J.), and Government Vellore Medical College (G.V.), Vellore, Kanchi Kamakoti Child Trust Hospital (B.S.), the National Institute of Epidemiology (G.K.C.P.), and the Institute of Child Health (P.D., M.J.), Chennai, Government Rajaji Hospital and Madurai Medical College, Madurai (K.M., H.B.), Coimbatore Medical College, Coimbatore (R.M., R. Gurusamy), the In- dian Council of Medical Research, New Delhi (S. Giri, I.P., M.D.G.), Translational Health Science and Technology Institute, Faridabad (R.A., G.K.), Kurnool Medical College and Government General Hospital, Kurnool (S.M.), Government General Hospital and Ranga- raya Medical College, Kakinada (K.B.G., B.R.), King George Hospital and Andhra Medical College, Visakhapatnam (P.P., R.P.G.), Sri Venkateshwara Medical College, Tirupati (M.B., V.M.), Sardar Valla Bhai Patel Post Graduate Institute of Paediatrics, Cuttack (S. Sath- pathy, H.M.), the Institute of Medical Sciences and SUM Hospital, Bhubaneswar (M.D.), Kalinga Institute of Medical Sciences (N.K.M.) and Hi-Tech Hospital (R.K.R., P.M.), Bhubaneswar, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak (G.G.), Shaheed Hasan Khan Mewati Government Medical College, Mewat (S.C.), Post Graduate Institute of Medical Education and Research, Chandigarh (M.G.), Sawai Man Singh Medical College, Jaipur (R. Gupta), Rabindranath Tagore Medical College, Udaipur (S. Goyal), Dr. Sampurnanand Medical College, Jodhpur (P.S.), Malankara Orthodox Syrian Church Medical College Hospital, Kolencherry (M.A.M.), Jawaharlal Nehru Institute of Post-graduate Medical Education and Research, Puducherry (S.K., A.S.), Mahatma Gandhi Memorial Medical College, Indore (H.J.), the Government Medical College, Guwahati, Assam (J.K.G.), King George Medical College, Lucknow (A.W.), and the Institute of Medical Sciences, Banaras Hindu University, Varanasi (V.G.) — all in India; and the Centers for Disease Control and Prevention, Atlanta (J.E.T., U.D.P.).
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Copyright © 2020 Massachusetts Medical Society.
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Copyright © 2020 Massachusetts Medical Society. All rights reserved. (TRUE COPY)
ANNEXURE: P2
17
18
19
20
21
22
23
24
25
26
27
28
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30
31
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35
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ANNEXURE: P4
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1st dose
2nd dose
3rd dose
Intussusception
intussusception by age
S.No
Date of birth Date Age in Days Date2 Age in Days3 Date4 Age in Days5 Date6 Age in Days7 Days since D1 Days since D2 Days since D3 Min(dsd1,dsd1,dsd1) without vaccination with vaccination
1 11/17/2018 12/22/2018 35 3/2/2019 105 3/30/2019 133 98 28 28 133
2 1/23/2017 8/30/2017 219 219 219
3 2/21/2017 6/18/2017 117 117 117
4 11/3/2018 6/4/2019 213 213 213
5 4/5/2016 3/1/2017 330 330 330
6 9/29/2017 12/14/2017 76 2/22/2018 146 3/22/2018 174 7/14/2018 288 212 142 114 114 288
7 2/19/2017 8/29/2017 191 191 191
8 3/17/2018 7/5/2018 110 110 110
9 1/23/2018 3/24/2018 60 4/24/2018 91 5/25/2018 122 8/26/2018 215 155 124 93 93 215
10 11/2/2017 2/21/2018 111 111 111
11 11/13/2016 10/10/2017 331 331 331
12 2/28/2017 8/15/2017 168 168 168
13 2/15/2017 8/9/2017 175 175 175
14 11/11/2017 1/10/2018 60 2/14/2018 95 3/14/2018 123 6/17/2018 218 158 123 95 95 218
15 9/27/2018 11/13/2018 47 1/5/2019 100 2/1/2019 127 3/31/2019 185 138 85 58 58 185
16 6/26/2017 8/16/2017 51 11/15/2017 142 1/3/2018 191 6/18/2018 357 306 215 166 166 357
17 4/19/2016 7/20/2016 92 8/17/2016 120 9/1/2016 135 43 15 15 135
18 10/16/2016 12/5/2016 50 1/9/2017 85 2/6/2017 113 4/14/2017 180 130 95 67 67 180
19 7/24/2017 9/20/2017 58 10/20/2017 88 11/22/2017 121 1/17/2018 177 119 89 56 56 177
20 4/18/2017 6/7/2017 50 7/15/2017 88 8/1/2017 105 55 17 17 105
21 9/1/2017 10/25/2017 54 12/13/2017 103 1/10/2018 131 1/13/2018 134 80 31 3 3 134
22 3/4/2019 4/18/2019 45 5/16/2019 73 6/24/2019 112 67 39 39 112
23 7/3/2017 11/22/2017 142 142 142
24 8/15/2018 10/1/2018 47 12/4/2018 111 12/26/2018 133 86 22 22 133
25 6/8/2015 6/6/2016 364 364 364
26 4/8/2018 5/23/2018 45 8/18/2018 132 10/3/2018 178 11/15/2018 221 176 89 43 43 221
27 11/12/2018 1/9/2019 58 2/13/2019 93 3/16/2019 124 66 31 31 124
28 4/17/2017 6/7/2017 51 7/5/2017 79 8/9/2017 114 9/26/2017 162 111 83 48 48 162
29 10/24/2016 12/28/2016 65 1/25/2017 93 2/22/2017 121 3/10/2017 137 72 44 16 16 137
30 10/3/2018 11/19/2018 47 12/19/2018 77 1/23/2019 112 5/2/2019 211 164 134 99 99 211
31 2/9/2016 4/6/2016 57 5/12/2016 93 6/1/2016 113 10/20/2016 254 197 161 141 141 254
32 3/22/2017 5/17/2017 56 6/28/2017 98 7/26/2017 126 8/11/2017 142 86 44 16 16 142
33 6/27/2017 8/17/2017 51 9/22/2017 87 10/26/2017 121 2/3/2018 221 170 134 100 100 221
34 5/2/2017 1/22/2018 265 265 265
35 3/6/2018 5/10/2018 65 6/14/2018 100 7/12/2018 128 12/16/2018 285 220 185 157 157 285
36 5/28/2017 7/12/2017 45 8/12/2017 76 9/27/2017 122 2/18/2018 266 221 190 144 144 266
37 7/8/2018 9/6/2018 60 10/20/2018 104 10/20/2018 104 44 0 0 104
38 3/7/2018 4/26/2018 50 7/3/2018 118 8/7/2018 153 1/11/2019 310 260 192 157 157 310
39 1/30/2017 4/5/2017 65 6/5/2017 126 61 61 126
40 6/12/2016 8/3/2016 52 10/5/2016 115 11/5/2016 146 11/19/2016 160 108 45 14 14 160
41 11/1/2017 4/25/2018 175 175 175
42 5/19/2018 11/4/2018 169 169 169
43 11/4/2018 12/20/2018 46 1/22/2019 79 2/22/2019 110 2/25/2019 113 67 34 3 3 113
44 10/16/2018 12/15/2018 60 1/9/2019 85 3/11/2019 146 86 61 61 146
45 12/21/2016 8/8/2017 230 230 230
46 4/19/2017 6/7/2017 49 7/5/2017 77 8/2/2017 105 10/2/2017 166 117 89 61 61 166
47 5/19/2016 7/6/2016 48 8/10/2016 83 9/14/2016 118 9/17/2016 121 73 38 3 3 121
48 10/23/2017 3/9/2018 137 137 137
49 2/12/2018 4/11/2018 58 5/2/2018 79 6/6/2018 114 7/24/2018 162 104 83 48 48 162
50 11/28/2017 1/18/2018 51 3/8/2018 100 4/5/2018 128 5/5/2018 158 107 58 30 30 158
51 10/18/2017 1/10/2018 84 2/14/2018 119 3/14/2018 147 3/14/2018 147 63 28 0 0 147
40
52 5/28/2016 8/3/2016 67 10/5/2016 130 11/23/2016 179 3/6/2017 282 215 152 103 103 282
53 8/8/2018 9/19/2018 42 10/17/2018 70 11/16/2018 100 2/9/2019 185 143 115 85 85 185
54 10/4/2018 4/11/2019 189 6/21/2019 260 71 71 260
55 10/11/2017 12/6/2017 56 1/17/2018 98 2/21/2018 133 9/8/2018 332 276 234 199 199 332
56 2/14/2018 1/10/2019 330 330 330
57 5/5/2017 3/16/2018 315 315 315
58 2/12/2018 4/4/2018 51 5/2/2018 79 6/6/2018 114 8/28/2018 197 146 118 83 83 197
59 10/17/2017 12/6/2017 50 1/24/2018 99 2/28/2018 134 3/9/2018 143 93 44 9 9 143
60 5/28/2017 7/18/2017 51 9/5/2017 100 10/3/2017 128 3/31/2018 307 256 207 179 179 307
61 6/10/2017 2/4/2018 239 239 239
62 5/9/2018 7/10/2018 62 8/23/2018 106 9/26/2018 140 12/6/2018 211 149 105 71 71 211
63 3/17/2017 12/27/2017 285 285 285
64 1/22/2017 11/24/2017 306 306 306
65 6/27/2017 10/5/2017 100 100 100
66 3/24/2019 5/16/2019 53 6/27/2019 95 7/14/2019 112 59 17 17 112
67 3/14/2017 5/3/2017 50 6/7/2017 85 7/21/2017 129 12/16/2017 277 227 192 148 148 277
68 10/15/2016 5/2/2017 199 199 199
69 1/1/2016 11/7/2016 311 311 311
70 12/13/2018 2/7/2019 56 3/7/2019 84 4/11/2019 119 7/19/2019 218 162 134 99 99 218
71 9/11/2018 11/1/2018 51 12/6/2018 86 2/7/2019 149 3/1/2019 171 120 85 22 22 171
72 8/12/2018 11/1/2018 81 2/7/2019 179 98 98 179
73 7/4/2018 8/23/2018 50 10/11/2018 99 2/5/2019 216 166 117 117 216
74 9/4/2018 10/17/2018 43 11/14/2018 71 12/19/2018 106 4/9/2019 217 174 146 111 111 217
75 10/8/2018 5/16/2019 220 220 220
78 8/17/2017 11/9/2017 84 12/14/2017 119 2/8/2018 175 3/27/2018 222 138 103 47 47 222
77 10/5/2016 12/14/2016 70 1/11/2017 98 2/8/2017 126 2/18/2017 136 66 38 10 10 136
78 12/19/2017 2/26/2018 69 3/27/2018 98 4/26/2018 128 7/13/2018 206 137 108 78 78 206
79 11/18/2017 1/2/2018 45 2/7/2018 81 3/7/2018 109 6/16/2018 210 165 129 101 101 210
80 12/16/2017 2/21/2018 67 4/18/2018 123 5/14/2018 149 82 26 26 149
81 12/8/2018 1/31/2019 54 3/7/2019 89 5/16/2019 159 6/21/2019 195 141 106 36 36 195
82 10/3/2018 11/24/2018 52 12/22/2018 80 1/25/2019 114 5/17/2019 226 174 146 112 112 226
83 5/22/2018 1/27/2019 250 250 250
84 1/23/2016 6/14/2016 143 143 143
85 10/25/2016 9/25/2017 335 335 335
86 4/5/2017 3/21/2018 350 350 350
87 9/3/2017 10/25/2017 52 11/22/2017 80 12/20/2017 108 4/16/2018 225 173 145 117 117 225
88 8/15/2016 10/19/2016 65 11/16/2016 93 12/21/2016 128 1/2/2017 140 75 47 12 12 140
89 7/10/2018 9/17/2018 69 10/15/2018 97 11/19/2018 132 4/29/2019 293 224 196 161 161 293
90 4/8/2016 11/3/2016 209 209 209
91 1/17/2017 3/8/2017 50 4/12/2017 85 5/10/2017 113 6/29/2017 163 113 78 50 50 163
92 9/25/2018 11/15/2018 51 12/20/2018 86 1/24/2019 121 5/28/2019 245 194 159 124 124 245
93 10/18/2018 12/3/2018 46 1/4/2019 78 5/6/2019 200 154 122 122 200
94 4/21/2016 11/20/2016 213 213 213
95 7/3/2017 8/16/2017 44 9/13/2017 72 10/11/2017 100 2/4/2018 216 172 144 116 116 216
96 9/9/2017 11/2/2017 54 12/13/2017 95 1/10/2018 123 5/11/2018 244 190 149 121 121 244
97 6/29/2018 9/19/2018 82 10/17/2018 110 11/22/2018 146 1/19/2019 204 122 94 58 58 204
98 12/6/2017 1/17/2018 42 2/20/2018 76 3/21/2018 105 7/20/2018 226 184 150 121 121 226
99 5/8/2018 12/11/2018 217 2/2/2019 270 53 53 270
100 10/18/2017 11/16/2017 29 12/21/2017 64 1/18/2018 92 8/29/2018 315 286 251 223 223 315
101 7/5/2018 8/20/2018 46 9/20/2018 77 11/21/2018 139 11/27/2018 145 99 68 6 6 145
102 12/6/2017 1/24/2018 49 2/28/2018 84 3/28/2018 112 7/11/2018 217 168 133 105 105 217
103 10/10/2018 12/6/2018 57 1/3/2019 85 3/28/2019 169 6/15/2019 248 191 163 79 79 248
104 5/16/2017 3/5/2018 293 293 293
105 9/5/2017 11/15/2017 71 12/20/2017 106 1/17/2018 134 4/20/2018 227 156 121 93 93 227
41
106 12/8/2017 2/3/2018 57 3/7/2018 89 3/10/2018 92 35 3 3 92
107 8/12/2017 10/4/2017 53 11/4/2017 84 12/13/2017 123 2/6/2018 178 125 94 55 55 178
108 5/9/2017 2/7/2018 274 274 274
109 6/24/2016 8/17/2016 54 9/21/2016 89 10/19/2016 117 4/2/2017 282 228 193 165 165 282
110 9/24/2017 11/9/2017 46 12/14/2017 81 1/18/2018 116 6/13/2018 262 216 181 146 146 262
111 8/1/2018 5/26/2019 298 298 298
112 10/20/2017 8/11/2018 295 295 295
113 6/29/2017 8/28/2017 60 10/9/2017 102 1/26/2018 211 151 109 109 211
114 6/23/2017 3/26/2018 276 276 276
115 6/3/2017 7/26/2017 53 8/30/2017 88 10/7/2017 126 2/4/2018 246 193 158 120 120 246
116 6/29/2017 9/6/2017 69 10/4/2017 97 11/1/2017 125 11/24/2017 148 79 51 23 23 148
117 5/15/2017 10/5/2017 143 12/11/2017 210 67 67 210
118 12/31/2016 10/26/2017 299 299 299
119 11/4/2018 1/2/2019 59 2/27/2019 115 3/28/2019 144 5/8/2019 185 126 70 41 41 185
120 9/22/2016 5/14/2017 234 234 234
121 12/20/2018 2/21/2019 63 3/22/2019 92 4/25/2019 126 6/27/2019 189 126 97 63 63 189
122 10/25/2018 12/12/2018 48 1/9/2019 76 2/13/2019 111 5/23/2019 210 162 134 99 99 210
123 5/31/2016 8/3/2016 64 9/7/2016 99 10/5/2016 127 5/29/2017 363 299 264 236 236 363
124 7/27/2017 3/5/2018 221 221 221
125 9/10/2018 11/21/2018 72 12/19/2018 100 1/16/2019 128 4/22/2019 224 152 124 96 96 224
126 8/21/2017 10/12/2017 52 12/28/2017 129 77 77 129
127 4/30/2018 6/20/2018 51 7/25/2018 86 9/12/2018 135 11/24/2018 208 157 122 73 73 208
128 4/27/2019 7/21/2019 85 85 85
129 10/31/2018 12/19/2018 49 1/30/2019 91 3/6/2019 126 7/1/2019 243 194 152 117 117 243
130 2/15/2018 4/24/2018 68 6/7/2018 112 12/10/2018 298 230 186 186 298
131 8/15/2015 5/8/2016 267 267 267
132 8/5/2017 10/5/2017 61 12/7/2017 124 1/4/2018 152 4/2/2018 240 179 116 88 88 240
133 1/25/2016 10/3/2016 252 252 252
134 10/28/2018 1/17/2019 81 3/14/2019 137 5/27/2019 211 130 74 74 211
135 2/13/2017 4/12/2017 58 5/19/2017 95 37 37 95
136 10/6/2017 11/22/2017 47 1/11/2018 97 2/8/2018 125 5/11/2018 217 170 120 92 92 217
137 1/1/2018 2/13/2018 43 3/14/2018 72 4/21/2018 110 7/7/2018 187 144 115 77 77 187
138 6/26/2016 8/17/2016 52 10/12/2016 108 11/16/2016 143 5/20/2017 328 276 220 185 185 328
139 7/24/2018 12/7/2018 136 136 136
140 5/3/2017 7/11/2017 69 8/11/2017 100 9/11/2017 131 10/22/2017 172 103 72 41 41 172
141 2/17/2018 4/11/2018 53 7/4/2018 137 8/1/2018 165 8/9/2018 173 120 36 8 8 173
142 2/5/2018 4/7/2018 61 5/5/2018 89 7/16/2018 161 10/12/2018 249 188 160 88 88 249
143 7/17/2017 10/5/2017 80 12/7/2017 143 1/4/2018 171 7/15/2018 363 283 220 192 192 363
144 10/18/2017 1/25/2018 99 3/22/2018 155 5/24/2018 218 6/3/2018 228 129 73 10 10 228
145 12/5/2017 2/8/2018 65 3/8/2018 93 4/12/2018 128 5/10/2018 156 91 63 28 28 156
146 10/31/2017 12/21/2017 51 1/18/2018 79 2/15/2018 107 6/1/2018 213 162 134 106 106 213
147 2/6/2016 9/12/2016 219 219 219
148 2/21/2019 7/3/2019 132 7/7/2019 136 4 4 136
149 11/4/2017 1/10/2018 67 2/28/2018 116 3/28/2018 144 5/19/2018 196 129 80 52 52 196
150 7/11/2017 11/23/2017 135 12/28/2017 170 1/25/2018 198 3/13/2018 245 110 75 47 47 245
151 10/3/2017 12/2/2017 60 2/2/2018 122 3/3/2018 151 91 29 29 151
152 2/5/2018 10/20/2018 257 257 257
153 2/13/2018 11/15/2018 275 275 275
154 5/24/2017 10/8/2017 137 137 137
155 12/20/2018 2/19/2019 61 3/14/2019 84 4/11/2019 112 7/26/2019 218 157 134 106 106 218
156 7/31/2017 12/16/2017 138 138 138
157 10/7/2018 5/1/2019 206 206 206
158 12/11/2015 5/10/2016 151 151 151
159 8/20/2017 10/7/2017 48 11/4/2017 76 12/2/2017 104 2/25/2018 189 141 113 85 85 189
42
160 5/14/2018 8/6/2018 84 9/6/2018 115 10/13/2018 152 12/20/2018 220 136 105 68 68 220
161 4/18/2018 9/26/2018 161 161 161
162 9/16/2018 11/21/2018 66 12/18/2018 93 1/16/2019 122 3/14/2019 179 113 86 57 57 179
163 10/11/2015 7/18/2016 281 281 281
164 5/19/2016 1/7/2017 233 233 233
165 5/28/2018 7/18/2018 51 8/29/2018 93 9/21/2018 116 9/21/2018 116 65 23 0 0 116
166 2/15/2017 9/25/2017 222 222 222
167 9/29/2017 11/15/2017 47 2/4/2018 128 81 81 128
168 9/1/2017 6/24/2018 296 296 296
169 7/15/2018 12/9/2018 147 147 147
170 1/19/2017 8/15/2017 208 208 208
171 3/12/2017 5/3/2017 52 6/21/2017 101 6/30/2017 110 58 9 9 110
172 7/9/2018 11/25/2018 139 139 139
173 10/29/2017 1/6/2018 69 2/3/2018 97 3/3/2018 125 5/16/2018 199 130 102 74 74 199
174 5/8/2017 6/21/2017 44 7/19/2017 72 8/16/2017 100 10/4/2017 149 105 77 49 49 149
175 8/18/2017 11/10/2017 84 12/11/2017 115 1/10/2018 145 3/29/2018 223 139 108 78 78 223
176 10/11/2018 3/21/2019 161 161 161
177 6/13/2018 8/1/2018 49 9/5/2018 84 10/10/2018 119 12/28/2018 198 149 114 79 79 198
178 10/29/2016 12/14/2016 46 1/11/2017 74 4/7/2017 160 6/21/2017 235 189 161 75 75 235
179 12/11/2017 2/21/2018 72 4/23/2018 133 5/30/2018 170 7/25/2018 226 154 93 56 56 226
180 7/14/2018 9/19/2018 67 10/24/2018 102 12/5/2018 144 12/10/2018 149 82 47 5 5 149
181 6/21/2017 8/23/2017 63 9/20/2017 91 10/25/2017 126 12/7/2017 169 106 78 43 43 169
182 4/28/2016 9/14/2016 139 10/6/2016 161 22 22 161
183 8/25/2017 10/9/2017 45 11/6/2017 73 12/7/2017 104 2/4/2018 163 118 90 59 59 163
184 7/23/2017 4/20/2018 271 271 271
185 5/20/2017 7/5/2017 46 8/2/2017 74 10/4/2017 137 1/14/2018 239 193 165 102 102 239
186 12/29/2016 9/2/2017 247 247 247
187 10/5/2017 12/5/2017 61 6/16/2018 254 193 193 254
188 12/10/2018 1/29/2019 50 3/8/2019 88 4/24/2019 135 6/5/2019 177 127 89 42 42 177
189 6/27/2017 9/6/2017 71 10/4/2017 99 11/1/2017 127 11/6/2017 132 61 33 5 5 132
190 1/17/2018 3/14/2018 56 5/9/2018 112 6/13/2018 147 7/13/2018 177 121 65 30 30 177
191 10/5/2018 4/18/2019 195 195 195
192 5/23/2017 7/12/2017 50 8/19/2017 88 9/22/2017 122 10/3/2017 133 83 45 11 11 133
193 6/8/2018 8/1/2018 54 9/5/2018 89 10/3/2018 117 11/10/2018 155 101 66 38 38 155
194 6/3/2018 8/8/2018 66 10/15/2018 134 11/14/2018 164 12/5/2018 185 119 51 21 21 185
195 9/8/2016 11/15/2016 68 12/14/2016 97 1/16/2017 130 1/31/2017 145 77 48 15 15 145
196 9/21/2016 11/9/2016 49 12/14/2016 84 1/11/2017 112 1/25/2017 126 77 42 14 14 126
197 5/8/2016 6/22/2016 45 7/27/2016 80 8/24/2016 108 11/13/2016 189 144 109 81 81 189
198 1/31/2018 3/21/2018 49 4/25/2018 84 5/24/2018 113 8/29/2018 210 161 126 97 97 210
199 10/10/2017 1/24/2018 106 2/28/2018 141 3/21/2018 162 56 21 21 162
200 1/10/2017 3/10/2017 59 4/12/2017 92 5/12/2017 122 6/8/2017 149 90 57 27 27 149
201 12/12/2018 1/30/2019 49 3/6/2019 84 4/10/2019 119 4/13/2019 122 73 38 3 3 122
202 8/30/2015 7/15/2016 320 320 320
203 3/8/2018 4/21/2018 44 5/19/2018 72 6/20/2018 104 7/30/2018 144 100 72 40 40 144
204 12/8/2018 2/20/2019 74 6/12/2019 186 112 112 186
205 9/24/2018 3/8/2019 165 4/20/2019 208 43 43 208
206 10/15/2017 12/6/2017 52 1/3/2018 80 2/7/2018 115 3/14/2018 150 98 70 35 35 150
207 3/26/2016 9/17/2016 175 175 175
208 9/9/2017 8/18/2018 343 343 343
209 8/3/2017 6/7/2018 308 308 308
210 5/8/2016 7/6/2016 59 8/3/2016 87 9/7/2016 122 11/7/2016 183 124 96 61 61 183
211 12/30/2017 2/14/2018 46 3/14/2018 74 4/11/2018 102 9/6/2018 250 204 176 148 148 250
212 10/31/2017 12/10/2017 40 1/15/2018 76 2/13/2018 105 5/15/2018 196 156 120 91 91 196
213 1/23/2019 4/20/2019 87 87 87
43
214 4/25/2016 6/15/2016 51 7/20/2016 86 8/18/2016 115 11/22/2016 211 160 125 96 96 211
215 11/27/2018 4/23/2019 147 147 147
216 9/5/2018 10/24/2018 49 11/29/2018 85 12/26/2018 112 2/11/2019 159 110 74 47 47 159
217 5/30/2017 7/19/2017 50 8/15/2017 77 9/20/2017 113 4/1/2018 306 256 229 193 193 306
218 4/26/2018 10/16/2018 173 173 173
219 6/5/2017 3/27/2018 295 295 295
220 8/27/2017 10/25/2017 59 12/9/2017 104 2/28/2018 185 3/28/2018 213 154 109 28 28 213
221 11/1/2018 3/24/2019 143 143 143
222 4/17/2017 6/14/2017 58 7/12/2017 86 9/13/2017 149 11/28/2017 225 167 139 76 76 225
223 8/10/2018 10/12/2018 63 11/11/2018 93 1/4/2019 147 1/8/2019 151 88 58 4 4 151
224 8/22/2015 8/1/2016 345 345 345
225 2/20/2018 4/10/2018 49 7/8/2018 138 89 89 138
226 8/12/2015 4/20/2016 252 252 252
227 11/8/2017 1/17/2018 70 2/21/2018 105 4/17/2018 160 8/1/2018 266 196 161 106 106 266
228 8/31/2017 10/25/2017 55 11/29/2017 90 12/16/2017 107 52 17 17 107
229 9/18/2017 6/6/2018 261 261 261
230 4/25/2017 6/16/2017 52 7/16/2017 82 8/31/2017 128 9/1/2017 129 77 47 1 1 129
231 6/26/2017 8/2/2017 37 9/5/2017 71 10/16/2017 112 6/8/2018 347 310 276 235 235 347
232 10/18/2016 12/21/2016 64 1/13/2017 87 2/15/2017 120 6/26/2017 251 187 164 131 131 251
233 9/16/2017 4/30/2018 226 226 226
234 9/20/2016 11/9/2016 50 12/14/2016 85 1/11/2017 113 3/20/2017 181 131 96 68 68 181
235 10/10/2016 11/23/2016 44 12/28/2016 79 1/25/2017 107 3/5/2017 146 102 67 39 39 146
236 10/6/2017 7/2/2018 269 269 269
237 3/23/2017 9/23/2017 184 184 184
238 1/15/2018 2/21/2018 37 3/21/2018 65 3/26/2018 70 33 5 5 70
239 12/3/2017 4/13/2018 131 131 131
240 11/14/2016 2/15/2017 93 2/18/2017 96 3/18/2017 124 6/6/2017 204 111 108 80 80 204
241 12/30/2017 2/21/2018 53 4/4/2018 95 5/9/2018 130 7/22/2018 204 151 109 74 74 204
242 11/19/2016 1/4/2017 46 3/1/2017 102 4/5/2017 137 7/22/2017 245 199 143 108 108 245
243 8/2/2017 10/28/2017 87 12/5/2017 125 3/17/2018 227 140 102 102 227
244 7/31/2018 10/12/2018 73 11/9/2018 101 12/14/2018 136 3/8/2019 220 147 119 84 84 220
245 3/9/2017 5/3/2017 55 6/28/2017 111 7/8/2017 121 66 10 10 121
246 5/1/2018 7/6/2018 66 8/7/2018 98 10/4/2018 156 1/16/2019 260 194 162 104 104 260
247 6/6/2017 7/24/2017 48 8/23/2017 78 9/20/2017 106 4/25/2018 323 275 245 217 217 323
248 11/15/2017 1/9/2018 55 2/12/2018 89 3/14/2018 119 6/23/2018 220 165 131 101 101 220
249 9/21/2017 4/19/2018 210 210 210
250 10/5/2018 12/8/2018 64 1/12/2019 99 3/6/2019 152 3/27/2019 173 109 74 21 21 173
251 7/19/2017 10/4/2017 77 12/8/2017 142 1/3/2018 168 91 26 26 168
252 7/26/2017 2/13/2018 202 202 202
253 8/31/2017 11/22/2017 83 1/10/2018 132 5/9/2018 251 6/28/2018 301 218 169 50 50 301
254 8/2/2016 10/5/2016 64 1/4/2017 155 2/1/2017 183 2/10/2017 192 128 37 9 9 192
255 10/23/2018 12/14/2018 52 1/18/2019 87 5/3/2019 192 140 105 105 192
256 12/24/2018 2/28/2019 66 5/5/2019 132 66 66 132
257 6/26/2017 8/16/2017 51 9/20/2017 86 3/29/2018 276 225 190 190 276
258 3/8/2016 4/20/2016 43 5/18/2016 71 6/15/2016 99 7/30/2016 144 101 73 45 45 144
259 9/18/2016 11/16/2016 59 12/21/2016 94 1/18/2017 122 4/11/2017 205 146 111 83 83 205
260 5/17/2017 7/8/2017 52 8/12/2017 87 9/9/2017 115 1/5/2018 233 181 146 118 118 233
261 9/16/2016 7/26/2017 313 313 313
262 2/27/2018 4/11/2018 43 5/9/2018 71 6/6/2018 99 6/20/2018 113 70 42 14 14 113
263 10/13/2016 12/3/2016 51 1/18/2017 97 2/22/2017 132 7/3/2017 263 212 166 131 131 263
264 5/5/2018 10/22/2018 170 170 170
265 9/23/2018 11/9/2018 47 12/12/2018 80 1/30/2019 129 5/4/2019 223 176 143 94 94 223
266 4/2/2017 5/29/2017 57 7/25/2017 114 9/29/2017 180 12/27/2017 269 212 155 89 89 269
267 8/28/2018 11/1/2018 65 12/6/2018 100 1/3/2019 128 7/19/2019 325 260 225 197 197 325
44
268 1/12/2018 2/28/2018 47 3/28/2018 75 4/25/2018 103 10/3/2018 264 217 189 161 161 264
269 10/27/2016 1/4/2017 69 2/1/2017 97 3/1/2017 125 3/1/2017 125 56 28 0 0 125
270 11/2/2017 12/19/2017 47 1/20/2018 79 2/15/2018 105 58 26 26 105
271 8/28/2016 10/19/2016 52 11/16/2016 80 12/21/2016 115 1/25/2017 150 98 70 35 35 150
272 2/6/2017 3/22/2017 44 4/26/2017 79 6/3/2017 117 73 38 38 117
273 12/25/2016 2/12/2017 49 3/12/2017 77 4/11/2017 107 11/30/2017 340 291 263 233 233 340
274 1/12/2017 3/22/2017 69 5/3/2017 111 6/21/2017 160 10/18/2017 279 210 168 119 119 279
275 12/23/2015 7/18/2016 208 208 208
276 2/25/2016 4/13/2016 48 5/14/2016 79 6/11/2016 107 9/1/2016 189 141 110 82 82 189
277 9/10/2017 5/16/2018 248 248 248
278 9/26/2016 11/16/2016 51 12/21/2016 86 1/18/2017 114 2/12/2017 139 88 53 25 25 139
279 1/4/2016 4/27/2016 114 5/28/2016 145 6/20/2016 168 54 23 23 168
280 3/4/2018 4/18/2018 45 5/16/2018 73 6/20/2018 108 8/20/2018 169 124 96 61 61 169
281 3/21/2017 9/3/2017 166 166 166
282 5/23/2016 7/13/2016 51 8/8/2016 77 26 26 77
283 11/28/2016 2/1/2017 65 4/5/2017 128 5/10/2017 163 9/2/2017 278 213 150 115 115 278
284 5/22/2018 9/2/2018 103 103 103
285 4/29/2018 8/5/2018 98 98 98
286 9/2/2017 11/8/2017 67 12/14/2017 103 1/10/2018 130 1/14/2018 134 67 31 4 4 134
287 9/22/2016 6/24/2017 275 275 275
288 5/10/2017 7/11/2017 62 8/17/2017 99 9/18/2017 131 12/1/2017 205 143 106 74 74 205
289 6/2/2017 7/19/2017 47 9/6/2017 96 11/8/2017 159 1/11/2018 223 176 127 64 64 223
290 11/29/2018 1/16/2019 48 2/20/2019 83 3/27/2019 118 4/26/2019 148 100 65 30 30 148
291 6/1/2018 9/30/2018 121 121 121
292 5/6/2018 7/3/2018 58 10/9/2018 156 1/6/2019 245 187 89 89 245
293 3/15/2016 6/22/2016 99 8/24/2016 162 10/24/2016 223 1/17/2017 308 209 146 85 85 308
294 7/26/2018 9/20/2018 56 10/25/2018 91 12/13/2018 140 4/8/2019 256 200 165 116 116 256
295 6/18/2018 8/10/2018 53 9/12/2018 86 10/17/2018 121 11/9/2018 144 91 58 23 23 144
296 6/12/2017 8/28/2017 77 10/1/2017 111 11/1/2017 142 3/15/2018 276 199 165 134 134 276
297 1/31/2017 3/15/2017 43 5/17/2017 106 6/21/2017 141 8/21/2017 202 159 96 61 61 202
298 3/22/2018 6/20/2018 90 90 90
299 4/26/2018 6/13/2018 48 7/18/2018 83 8/29/2018 125 3/2/2019 310 262 227 185 185 310
300 8/23/2017 10/7/2017 45 11/4/2017 73 12/2/2017 101 7/4/2018 315 270 242 214 214 315
301 9/22/2016 3/1/2017 160 160 160
302 8/12/2018 9/14/2018 33 10/7/2018 56 12/26/2018 136 3/25/2019 225 192 169 89 89 225
303 10/6/2018 11/22/2018 47 12/27/2018 82 2/7/2019 124 7/19/2019 286 239 204 162 162 286
304 7/28/2017 4/10/2018 256 256 256
305 9/6/2017 11/8/2017 63 12/8/2017 93 1/10/2018 126 6/10/2018 277 214 184 151 151 277
306 10/27/2018 12/27/2018 61 1/24/2019 89 3/28/2019 152 4/29/2019 184 123 95 32 32 184
307 10/12/2018 3/19/2019 158 158 158
308 7/12/2016 9/16/2016 66 11/16/2016 127 12/16/2016 157 12/20/2016 161 95 34 4 4 161
309 9/2/2018 11/21/2018 80 12/19/2018 108 1/16/2019 136 3/23/2019 202 122 94 66 66 202
310 11/28/2017 2/1/2018 65 3/4/2018 96 3/30/2018 122 57 26 26 122
311 8/16/2018 2/25/2019 193 193 193
312 1/23/2018 3/8/2018 44 6/7/2018 135 8/26/2018 215 9/16/2018 236 192 101 21 21 236
313 1/4/2018 3/17/2018 72 4/14/2018 100 7/14/2018 191 10/13/2018 282 210 182 91 91 282
314 7/13/2017 9/20/2017 69 10/18/2017 97 2/21/2018 223 4/20/2018 281 212 184 58 58 281
315 8/24/2016 10/15/2016 52 11/19/2016 87 1/7/2017 136 5/22/2017 271 219 184 135 135 271
316 10/28/2015 6/29/2016 245 245 245
317 8/12/2016 12/13/2016 123 2/14/2017 186 3/11/2017 211 7/24/2017 346 223 160 135 135 346
318 8/24/2017 12/1/2017 99 1/5/2018 134 2/5/2018 165 66 31 31 165
319 9/9/2017 10/25/2017 46 11/22/2017 74 12/20/2017 102 3/30/2018 202 156 128 100 100 202
320 3/18/2016 1/14/2017 302 302 302
321 8/13/2018 10/8/2018 56 11/22/2018 101 1/5/2019 145 89 44 44 145
45
322 3/15/2016 8/25/2016 163 163 163
323 11/25/2016 1/11/2017 47 2/8/2017 75 3/8/2017 103 11/18/2017 358 311 283 255 255 358
324 7/28/2017 1/2/2018 158 158 158
?25 10/10/2016 12/1/2016 52 1/17/2017 99 2/23/2017 136 6/9/2017 242 190 143 106 106 242
326 11/9/2018 1/2/2019 54 2/6/2019 89 3/13/2019 124 4/23/2019 165 111 76 41 41 165
327 12/8/2017 1/31/2018 54 2/28/2018 82 3/28/2018 110 4/7/2018 120 66 38 10 10 120
328 4/3/2018 5/23/2018 50 6/27/2018 85 8/1/2018 120 10/23/2018 203 153 118 83 83 203
329 12/5/2018 1/18/2019 44 2/20/2019 77 4/10/2019 126 4/26/2019 142 98 65 16 16 142
330 12/29/2018 6/18/2019 171 171 171
331 9/8/2017 10/25/2017 47 12/14/2017 97 1/15/2018 129 5/6/2018 240 193 143 111 111 240
332 5/29/2017 7/13/2017 45 2/13/2018 260 215 215 260
333 5/27/2018 7/11/2018 45 8/18/2018 83 9/19/2018 115 12/10/2018 197 152 114 82 82 197
334 12/14/2016 11/25/2017 346 346 346
335 2/1/2017 3/23/2017 50 4/21/2017 79 6/12/2017 131 10/2/2017 243 193 164 112 112 243
336 11/28/2017 1/27/2018 60 2/14/2018 78 3/14/2018 106 8/23/2018 268 208 190 162 162 268
337 12/4/2017 5/20/2018 167 167 167
338 1/22/2018 3/10/2018 47 4/12/2018 80 5/17/2018 115 8/20/2018 210 163 130 95 95 210
339 8/20/2018 10/10/2018 51 11/14/2018 86 12/12/2018 114 1/25/2019 158 107 72 44 44 158
340 7/21/2016 6/4/2017 318 318 318
341 12/13/2017 4/18/2018 126 8/30/2018 260 134 134 260
342 5/17/2017 7/5/2017 49 8/2/2017 77 8/30/2017 105 3/11/2018 298 249 221 193 193 298
343 9/2/2017 10/25/2017 53 4/5/2018 215 162 162 215
344 7/22/2017 4/4/2018 256 256 256
345 7/10/2016 9/13/2016 65 10/11/2016 93 10/22/2016 104 39 11 11 104
346 3/30/2017 10/21/2017 205 205 205
347 5/4/2016 6/26/2016 53 8/8/2016 96 9/7/2016 126 2/28/2017 300 247 204 174 174 300
348 11/7/2017 5/9/2018 183 183 183
349 9/17/2018 6/18/2019 274 274 274
350 1/11/2018 2/28/2018 48 3/28/2018 76 4/25/2018 104 6/26/2018 166 118 90 62 62 166
351 8/21/2017 10/7/2017 47 11/18/2017 89 11/26/2017 97 50 8 8 97
352 5/16/2016 1/14/2017 243 243 243
353 10/12/2018 2/2/2019 113 5/20/2019 220 107 107 220
354 4/26/2017 6/14/2017 49 7/17/2017 82 8/28/2017 124 3/13/2018 321 272 239 197 197 321
355 5/6/2016 6/29/2016 54 8/3/2016 89 9/7/2016 124 12/5/2016 213 159 124 89 89 213
356 12/19/2017 1/31/2018 43 2/28/2018 71 3/28/2018 99 5/23/2018 155 112 84 56 56 155
357 12/11/2017 1/28/2018 48 2/28/2018 79 3/28/2018 107 8/8/2018 240 192 161 133 133 240
358 6/27/2018 8/20/2018 54 9/19/2018 84 10/24/2018 119 12/9/2018 165 111 81 46 46 165
359 11/13/2018 12/27/2018 44 2/6/2019 85 3/6/2019 113 5/17/2019 185 141 100 72 72 185
360 12/12/2017 1/29/2018 48 3/7/2018 85 4/11/2018 120 7/13/2018 213 165 128 93 93 213
361 4/16/2017 5/31/2017 45 6/28/2017 73 7/26/2017 101 4/16/2018 365 320 292 264 264 365
362 6/1/2017 3/20/2018 292 292 292
363 12/26/2016 6/27/2017 183 183 183
364 10/10/2016 5/30/2017 232 232 232
365 3/12/2017 9/26/2017 198 198 198
366 11/1/2016 6/27/2017 238 238 238
367 6/12/2018 1/22/2019 224 224 224
368 6/16/2017 3/21/2018 278 278 278
369 8/11/2017 9/27/2017 47 10/25/2017 75 12/6/2017 117 6/16/2018 309 262 234 192 192 309
370 8/9/2018 5/26/2019 290 290 290
371 4/6/2016 5/18/2016 42 6/22/2016 77 3/30/2017 358 316 281 281 358
372 7/2/2018 9/12/2018 72 11/10/2018 131 1/23/2019 205 2/17/2019 230 158 99 25 25 230
373 7/4/2018 9/19/2018 77 10/17/2018 105 11/22/2018 141 1/2/2019 182 105 77 41 41 182
374 5/4/2017 1/7/2018 248 248 248
375 4/19/2016 6/18/2016 60 7/23/2016 95 8/20/2016 123 1/8/2017 264 204 169 141 141 264
46
376 11/3/2017 12/19/2017 46 1/30/2018 88 3/3/2018 120 6/5/2018 214 168 126 94 94 214
377 10/19/2018 12/12/2018 54 3/13/2019 145 4/10/2019 173 5/19/2019 212 158 67 39 39 212
378 2/15/2018 4/4/2018 48 5/2/2018 76 6/6/2018 111 8/23/2018 189 141 113 78 78 189
379 5/26/2017 5/3/2018 342 342 342
380 4/19/2017 10/5/2017 169 169 169
381 10/25/2016 9/18/2017 328 328 328
382 11/4/2018 12/19/2018 45 1/23/2019 80 2/27/2019 115 6/5/2019 213 168 133 98 98 213
383 8/19/2017 6/19/2018 304 304 304
384 6/28/2016 4/5/2017 281 281 281
385 7/27/2017 1/16/2018 173 173 173
386 1/11/2019 4/3/2019 82 4/11/2019 90 8 8 90
387 5/13/2018 6/27/2018 45 8/1/2018 80 9/5/2018 115 11/9/2018 180 135 100 65 65 180
388 4/15/2018 6/5/2018 51 12/8/2018 237 186 186 237
389 10/7/2017 10/3/2018 361 361 361
390 2/4/2018 4/19/2018 74 5/24/2018 109 6/28/2018 144 7/26/2018 172 98 63 28 28 172
391 3/20/2017 5/13/2017 54 7/12/2017 114 10/8/2017 202 148 88 88 202
392 2/27/2018 2/1/2019 339 339 339
393 9/7/2018 2/16/2019 162 162 162
394 11/19/2017 11/4/2018 350 350 350
395 10/15/2018 12/5/2018 51 1/2/2019 79 2/18/2019 126 6/14/2019 242 191 163 116 116 242
396 11/16/2017 5/29/2018 194 194 194
397 4/16/2018 6/6/2018 51 7/4/2018 79 8/8/2018 114 4/13/2019 362 311 283 248 248 362
398 6/24/2017 8/14/2017 51 9/26/2017 94 10/30/2017 128 3/19/2018 268 217 174 140 140 268
399 6/21/2016 11/29/2016 161 161 161
400 8/6/2018 9/21/2018 46 10/20/2018 75 11/24/2018 110 6/13/2019 311 265 236 201 201 311
401 3/29/2018 5/17/2018 49 7/2/2018 95 7/30/2018 123 74 28 28 123
402 8/4/2018 3/31/2019 239 239 239
403 8/13/2018 9/28/2018 46 4/18/2019 248 202 202 248
404 6/2/2017 4/14/2018 316 316 316
405 8/10/2017 5/13/2018 276 276 276
406 12/6/2017 7/30/2018 236 236 236
407 11/8/2017 5/27/2018 200 200 200
408 5/31/2018 7/18/2018 48 8/24/2018 85 9/26/2018 118 4/17/2019 321 273 236 203 203 321
409 11/29/2016 9/6/2017 281 281 281
410 5/10/2017 7/3/2017 54 8/5/2017 87 9/5/2017 118 1/3/2018 238 184 151 120 120 238
411 6/23/2018 8/5/2018 43 9/15/2018 84 10/14/2018 113 2/28/2019 250 207 166 137 137 250
412 8/16/2017 10/11/2017 56 11/16/2017 92 12/20/2017 126 3/12/2018 208 152 116 82 82 208
413 1/11/2017 12/2/2017 325 325 325
414 1/26/2016 9/28/2016 246 246 246
415 3/24/2018 5/17/2018 54 6/20/2018 88 7/26/2018 124 12/23/2018 274 220 186 150 150 274
416 10/13/2016 2/24/2017 134 134 134
417 8/17/2018 10/3/2018 47 11/7/2018 82 12/15/2018 120 12/18/2018 123 76 41 3 3 123
418 11/17/2017 6/6/2018 201 201 201
419 3/9/2018 5/7/2018 59 6/4/2018 87 7/2/2018 115 11/13/2018 249 190 162 134 134 249
420 9/28/2017 11/17/2017 50 12/21/2017 84 2/6/2018 131 5/20/2018 234 184 150 103 103 234
421 9/29/2017 12/13/2017 75 4/24/2018 207 132 132 207
422 9/6/2018 10/27/2018 51 11/24/2018 79 12/24/2018 109 2/20/2019 167 116 88 58 58 167
42* 10/6/2016 11/23/2016 48 12/28/2016 83 1/25/2017 111 6/9/2017 246 198 163 135 135 246
424 2/28/2017 4/12/2017 43 5/24/2017 85 7/3/2017 125 82 40 40 125
425 1/2/2016 2/17/2016 46 3/28/2016 86 5/6/2016 125 11/6/2016 309 263 223 184 184 309
426 7/3/2017 4/19/2018 290 290 290
427 8/31/2016 11/16/2016 77 12/21/2016 112 1/18/2017 140 7/30/2017 333 256 221 193 193 333
428 12/23/2016 8/23/2017 243 243 243
429 3/11/2017 5/6/2017 56 6/3/2017 84 7/1/2017 112 2/10/2018 336 280 252 224 224 336
47
430 8/10/2018 9/26/2018 47 10/31/2018 82 11/28/2018 110 12/20/2018 132 85 50 22 22 132
431 7/26/2017 12/21/2017 148 1/25/2018 183 2/21/2018 210 7/1/2018 340 192 157 130 130 340
432 6/22/2016 1/20/2017 212 212 212
433 3/1/2017 8/2/2017 154 154 154
434 11/26/2017 1/17/2018 52 2/28/2018 94 3/21/2018 115 6/19/2018 205 153 111 90 90 205
435 10/13/2017 12/8/2017 56 1/12/2018 91 2/21/2018 131 2/27/2018 137 81 46 6 6 137
436 12/30/2017 3/8/2018 68 4/4/2018 95 5/5/2018 126 8/27/2018 240 172 145 114 114 240
437 4/22/2017 12/29/2017 251 251 251
438 7/18/2016 9/28/2016 72 10/26/2016 100 11/23/2016 128 3/31/2017 256 184 156 128 128 256
439 3/4/2016 4/17/2016 44 6/23/2016 111 8/4/2016 153 1/1/2017 303 259 192 150 150 303
440 11/11/2017 2/20/2018 101 101 101
441 4/18/2016 3/21/2017 337 337 337
442 7/11/2017 3/31/2018 263 263 263
443 11/25/2017 1/17/2018 53 2/28/2018 95 3/28/2018 123 9/11/2018 290 237 195 167 167 290
444 12/27/2017 2/18/2018 53 3/19/2018 82 4/19/2018 113 7/7/2018 192 139 110 79 79 192
445 8/2/2017 3/25/2018 235 235 235
446 11/23/2016 12/28/2016 35 1/28/2017 66 3/1/2017 98 7/8/2017 227 192 161 129 129 227
447 8/25/2018 10/10/2018 46 11/21/2018 88 12/26/2018 123 4/15/2019 233 187 145 110 110 233
448 7/23/2017 10/29/2017 98 98 98
449 7/3/2017 2/18/2018 230 230 230
450 5/18/2018 2/28/2019 286 286 286
451 9/27/2018 11/16/2018 50 12/19/2018 83 2/6/2019 132 5/30/2019 245 195 162 113 113 245
452 7/9/2016 9/21/2016 74 11/9/2016 123 12/21/2016 165 5/15/2017 310 236 187 145 145 310
453 1/14/2018 6/5/2018 142 142 142
454 11/21/2017 1/17/2018 57 2/21/2018 92 3/21/2018 120 4/26/2018 156 99 64 36 36 156
455 7/25/2018 9/20/2018 57 10/25/2018 92 12/5/2018 133 5/22/2019 301 244 209 168 168 301
456 8/25/2017 5/5/2018 253 253 253
457 6/28/2017 3/12/2018 257 257 257
458 3/18/2018 5/2/2018 45 6/13/2018 87 7/11/2018 115 10/9/2018 205 160 118 90 90 205
459 7/31/2016 1/27/2017 180 180 180
460 5/16/2016 9/7/2016 114 12/8/2016 206 92 92 206
461 11/9/2017 2/21/2018 104 3/21/2018 132 4/4/2018 146 42 14 14 146
462 1/15/2018 3/6/2018 50 4/4/2018 79 5/2/2018 107 6/30/2018 166 116 87 59 59 166
463 8/8/2017 10/4/2017 57 11/8/2017 92 2/28/2018 204 147 112 112 204
464 7/5/2018 5/31/2019 330 330 330
465 2/15/2019 4/2/2019 46 4/15/2019 59 13 13 59
466 7/29/2017 1/20/2018 175 175 175
467 4/1/2018 5/16/2018 45 7/11/2018 101 8/1/2018 122 77 21 21 122
468 4/7/2018 1/17/2019 285 285 285
469 9/5/2016 11/15/2016 71 12/14/2016 100 1/16/2017 133 5/5/2017 242 171 142 109 109 242
470 10/15/2016 11/22/2016 38 12/21/2016 67 1/26/2017 103 3/7/2017 143 105 76 40 40 143
471 8/31/2017 5/20/2018 262 262 262
472 12/8/2017 2/14/2018 68 3/21/2018 103 5/2/2018 145 7/12/2018 216 148 113 71 71 216
473 9/10/2016 7/12/2017 305 305 305
474 9/25/2017 4/6/2018 193 193 193
475 10/23/2017 12/13/2017 51 2/14/2018 114 4/18/2018 177 7/2/2018 252 201 138 75 75 252
476 8/10/2017 5/10/2018 273 273 273
477 6/15/2018 8/16/2018 62 9/19/2018 96 10/25/2018 132 6/4/2019 354 292 258 222 222 354
478 6/17/2016 10/19/2016 124 124 124
479 11/6/2017 1/10/2018 65 2/21/2018 107 3/21/2018 135 6/19/2018 225 160 118 90 90 225
480 9/5/2018 2/20/2019 168 168 168
481 11/11/2018 1/2/2019 52 2/6/2019 87 3/13/2019 122 4/3/2019 143 91 56 21 21 143
482 9/17/2016 1/17/2017 122 122 122
483 1/12/2018 8/1/2018 201 201 201
48
484 4/24/2017 7/12/2017 79 8/9/2017 107 9/13/2017 142 10/17/2017 176 97 69 34 34 176
485 3/27/2018 9/21/2018 178 178 178
486 5/3/2018 6/20/2018 48 7/23/2018 81 8/23/2018 112 9/19/2018 139 91 58 27 27 139
487 2/2/2017 8/28/2017 207 207 207
488 4/27/2018 4/22/2019 360 360 360
489 4/3/2017 1/19/2018 291 291 291
490 6/19/2017 9/7/2017 80 80 80
491 8/14/2017 5/2/2018 261 261 261
492 2/3/2017 12/14/2017 314 314 314
493 10/8/2017 6/4/2018 239 239 239
494 8/12/2017 6/17/2018 309 309 309
495 12/10/2017 1/24/2018 45 2/28/2018 80 4/4/2018 115 5/31/2018 172 127 92 57 57 172
496 2/7/2017 9/23/2017 228 228 228
497 3/26/2018 6/6/2018 72 7/4/2018 100 8/1/2018 128 1/22/2019 302 230 202 174 174 302
498 4/19/2018 6/28/2018 70 7/26/2018 98 8/23/2018 126 11/21/2018 216 146 118 90 90 216
499 5/7/2018 4/3/2019 331 331 331
500 3/8/2018 5/10/2018 63 6/14/2018 98 7/12/2018 126 12/2/2018 269 206 171 143 143 269
501 8/9/2018 3/24/2019 227 227 227
502 3/19/2018 5/7/2018 49 6/8/2018 81 7/8/2018 111 7/24/2018 127 78 46 16 16 127
503 7/1/2016 2/26/2017 240 240 240
504 8/5/2016 11/22/2016 109 109 109
505 7/3/2017 10/31/2017 120 120 120
506 2/27/2018 5/10/2018 72 6/14/2018 107 7/12/2018 135 11/22/2018 268 196 161 133 133 268
507 10/7/2017 5/10/2018 215 215 215
508 5/8/2018 7/4/2018 57 8/1/2018 85 10/3/2018 148 1/6/2019 243 186 158 95 95 243
509 3/13/2017 5/5/2017 53 6/9/2017 88 7/10/2017 119 2/24/2018 348 295 260 229 229 348
510 10/13/2016 4/22/2017 191 191 191
511 4/3/2017 2/10/2018 313 313 313
512 10/26/2017 2/14/2018 111 7/15/2018 262 151 151 262
513 11/27/2018 1/23/2019 57 3/6/2019 99 4/3/2019 127 6/14/2019 199 142 100 72 72 199
514 1/29/2018 3/14/2018 44 4/11/2018 72 5/16/2018 107 6/26/2018 148 104 76 41 41 148
515 11/26/2017 2/1/2018 67 3/8/2018 102 5/10/2018 165 5/12/2018 167 100 65 2 2 167
516 8/5/2016 4/14/2017 252 252 252
517 1/29/2018 3/21/2018 51 4/25/2018 86 9/7/2018 221 170 135 135 221
518 2/2/2018 4/4/2018 61 5/23/2018 110 8/13/2018 192 131 82 82 192
519 6/6/2018 7/28/2018 52 8/25/2018 80 9/28/2018 114 3/28/2019 295 243 215 181 181 295
520 11/16/2017 1/10/2018 55 2/14/2018 90 4/23/2018 158 103 68 68 158
521 7/26/2017 9/13/2017 49 10/12/2017 78 11/13/2017 110 12/10/2017 137 88 59 27 27 137
522 6/20/2018 8/3/2018 44 11/13/2018 146 102 102 146
523 5/15/2018 4/22/2019 342 342 342
524 11/6/2018 5/12/2019 187 187 187
525 2/16/2017 4/20/2017 63 5/18/2017 91 7/20/2017 154 11/22/2017 279 216 188 125 125 279
526 2/17/2017 10/29/2017 254 254 254
527 8/30/2018 11/5/2018 67 12/5/2018 97 1/16/2019 139 2/9/2019 163 96 66 24 24 163
528 10/6/2017 4/11/2018 187 187 187
529 3/17/2017 5/8/2017 52 6/9/2017 84 7/10/2017 115 1/5/2018 294 242 210 179 179 294
530 12/4/2015 10/16/2016 317 317 317
531 7/11/2017 9/7/2017 58 10/5/2017 86 11/2/2017 114 12/16/2017 158 100 72 44 44 158
532 3/17/2018 5/5/2018 49 6/6/2018 81 7/18/2018 123 9/22/2018 189 140 108 66 66 189
533 8/12/2018 3/2/2019 202 202 202
534 8/1/2017 9/21/2017 51 10/26/2017 86 12/7/2017 128 1/14/2018 166 115 80 38 38 166
535 2/7/2017 4/13/2017 65 5/14/2017 96 7/24/2017 167 12/9/2017 305 240 209 138 138 305
536 7/10/2017 8/23/2017 44 9/27/2017 79 10/25/2017 107 12/21/2017 164 120 85 57 57 164
537 11/16/2016 10/24/2017 342 342 342
49
538 5/30/2018 11/8/2018 162 162 162
539 12/28/2017 3/24/2018 86 86 86
540 5/20/2017 8/21/2017 93 10/27/2017 160 67 67 160
541 10/26/2017 12/13/2017 48 12/18/2017 53 5 5 53
542 8/24/2017 2/20/2018 180 180 180
543 3/10/2019 4/27/2019 48 48 48
544 2/15/2016 4/12/2016 57 5/18/2016 93 6/14/2016 120 1/11/2017 331 274 238 211 211 331
545 4/29/2017 2/7/2018 284 284 284
546 7/17/2017 1/27/2018 194 194 194
547 2/9/2018 4/4/2018 54 5/2/2018 82 6/6/2018 117 6/20/2018 131 77 49 14 14 131
548 1/20/2018 3/14/2018 53 5/19/2018 119 6/16/2018 147 8/16/2018 208 155 89 61 61 208
549 1/16/2018 3/1/2018 44 44 44
550 9/16/2018 12/10/2018 85 1/5/2019 111 1/6/2019 112 27 1 1 112
551 6/20/2017 3/14/2018 267 267 267
552 1/12/2018 3/21/2018 68 68 68
553 10/14/2017 3/31/2018 168 168 168
554 12/3/2017 1/24/2018 52 2/28/2018 87 3/10/2018 97 45 10 10 97
555 4/8/2017 12/19/2017 255 255 255
556 7/17/2018 1/11/2019 178 178 178
557 3/18/2017 10/23/2017 219 1/22/2018 310 91 91 310
558 10/5/2018 12/12/2018 68 1/12/2019 99 1/29/2019 116 48 17 17 116
559 10/8/2017 11/24/2017 47 12/28/2017 81 1/25/2018 109 3/14/2018 157 110 76 48 48 157
560 9/4/2016 10/13/2016 39 12/10/2016 97 12/12/2016 99 60 2 2 99
561 1/2/2017 2/23/2017 52 3/27/2017 84 32 32 84
562 8/1/2017 9/19/2017 49 10/18/2017 78 12/5/2017 126 77 48 48 126
563 4/3/2018 5/28/2018 55 6/28/2018 86 8/2/2018 121 9/17/2018 167 112 81 46 46 167
564 5/15/2018 7/7/2018 53 8/18/2018 95 10/16/2018 154 101 59 59 154
565 10/7/2018 12/6/2018 60 1/9/2019 94 2/14/2019 130 5/10/2019 215 155 121 85 85 215
566 7/6/2018 8/22/2018 47 9/24/2018 80 10/24/2018 110 3/20/2019 257 210 177 147 147 257
567 5/16/2018 7/11/2018 56 8/8/2018 84 10/19/2018 156 100 72 72 156
568 10/3/2017 5/3/2018 212 212 212
569 4/5/2018 6/13/2018 69 7/11/2018 97 8/8/2018 125 9/13/2018 161 92 64 36 36 161
570 2/10/2017 3/26/2017 44 4/29/2017 78 5/30/2017 109 9/26/2017 228 184 150 119 119 228
571 2/16/2017 9/15/2017 211 211 211
572 1/7/2019 3/20/2019 72 4/17/2019 100 5/15/2019 128 6/18/2019 162 90 62 34 34 162
573 7/7/2016 9/3/2016 58 10/4/2016 89 10/13/2016 98 40 9 9 98
574 4/27/2018 10/13/2018 169 169 169
575 11/7/2015 6/9/2016 215 215 215
576 2/8/2017 4/5/2017 56 5/6/2017 87 6/3/2017 115 1/4/2018 330 274 243 215 215 330
577 11/24/2018 3/8/2019 104 4/12/2019 139 6/14/2019 202 7/3/2019 221 117 82 19 19 221
578 2/20/2018 4/26/2018 65 5/24/2018 93 6/21/2018 121 7/18/2018 148 83 55 27 27 148
579 10/8/2016 12/3/2016 56 2/3/2017 118 3/15/2017 158 5/20/2017 224 168 106 66 66 224
580 6/23/2016 9/3/2016 72 10/1/2016 100 11/5/2016 135 11/6/2016 136 64 36 1 1 136
581 12/11/2018 2/13/2019 64 64 64
582 10/22/2016 1/19/2017 89 89 89
583 5/26/2017 5/20/2018 359 359 359
584 5/2/2017 6/19/2017 48 7/20/2017 79 8/25/2017 115 12/29/2017 241 193 162 126 126 241
585 9/24/2017 5/4/2018 222 222 222
586 9/11/2018 11/7/2018 57 12/9/2018 89 1/2/2019 113 2/14/2019 156 99 67 43 43 156
587 7/4/2018 8/21/2018 48 9/26/2018 84 10/15/2018 103 55 19 19 103
588 12/22/2018 2/6/2019 46 3/13/2019 81 6/5/2019 165 119 84 84 165
589 6/6/2017 9/27/2017 113 2/10/2018 249 136 136 249
50
Count (N) 212 377 Difference -17.89
Mean 223.25 205.36 SE 5.915
Standard Deviation
74.12
65.8
95%CI -29.508
to -6.272
Mean Difference
17.89 Test Statistic t
-3.024
Signiï¬cance level (p=)
0.0026
DF
587
Signiï¬cance level
p=0.0026
(TRUE COPY)
ANNEXURE: P5 51
From: NEJM Letter <onbehalfof@manuscriptcentral.com> Date: Thu, 20 May 2021, 11:36 pm
Subject: New England Journal of Medicine 20-33556 To: <jacob@puliyel.com>
Dear Dr. Puliyel:
Thank you for your email. We have been in contact with Dr. Kang regarding your letter, and the correspondence remains under consideration. You will be informed of the final editorial decision via email.
Sincerely,
Lauren Lindenfelser
Manager of Editorial Administration
New England Journal of Medicine 10 Shattuck Street
Boston, MA 02115
(617) 734-9800
Fax: (617) 739-9864
http://www.nejm.org
From: Jacob Puliyel <jacob@puliyel.com> Sent: Tuesday, May 4, 2021 3:13 PM
To: Letter <letter@nejm.org>
Subject: Re: New England Journal of Medicine - 20-33556
Dear Sir
I am yet to receive a response from the Editor.
If no action is being taken by the NEJM in all these months,
I wonder if the matter should be investigated by some independent third party like Retraction Watch.
Please advise me when I should expect a response from the Editor or otherwise what I should do to get this matter investigated.
Sincerely Jacob Puliyel
(TRUE COPY)