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opensafely / immunosuppressant-meds-research

This repo is to support investigations into immunosuppressant medications and COVID-19 outcomes
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Stata code for analysis #31

Closed myatesrheum closed 3 years ago

myatesrheum commented 3 years ago

ssc install table1_mc ssc install blindschemes set scheme plotplainblind ssc install asdoc

import delimited "$datac\input (2).csv", clear

/ SET Index date ===========================================================/ global indexdate = "01/03/2020"

/ RENAME VARIABLES===========================================================/

rename inflammatory_bowel_disease_uncla ibd_uncla

/ Drop variables not needed ================================================/ *calculating ckd from creat drop ckd

/ CONVERT STRINGS TO DATE====================================================/ / Comorb dates are given with month/year only, so adding day 15 to enable them to be processed as dates /

foreach var of varlist crohns_disease /// ulcerative_colitis /// ibd_uncla /// atopic_dermatitis /// psoriasis /// hidradenitis_suppurativa /// psoriatic_arthritis /// rheumatoid_arthritis /// ankylosing_spondylitis /// chronic_cardiac_disease /// hba1c_new /// hba1c_old /// hba1c_mmol_per_mol_date /// hba1c_percentage_date /// diabetes /// hypertension /// chronic_respiratory_disease /// esrf /// copd /// chronic_liver_disease /// stroke /// lung_cancer /// haem_cancer /// other_cancer /// creatinine_date /// organ_transplant /// bmi_date_measured /// oral_prednisolone_earliest /// oral_prednisolone_latest /// anti_tnf_earliest /// anti_tnf_latest /// anti_il6_earliest /// anti_il6_latest /// anti_il1223_earliest /// anti_il1223_latest /// anti_il1_earliest /// anti_il1_latest /// anti_il4_earliest /// anti_il4_latest /// jak_inhibitors_earliest /// jak_inhibitors_latest /// rituximab_earliest /// rituximab_latest /// anti_integrin_earliest /// anti_integrin_latest /// azathioprine_earliest /// azathioprine_latest /// ciclosporin_earliest /// ciclosporin_latest /// gold_earliest /// gold_latest /// leflunomide_earliest /// leflunomide_latest /// mercaptopurine_earliest /// mercaptopurine_latest /// methotrexate_earliest /// methotrexate_latest /// mycophenolate_earliest /// mycophenolate_latest /// penicillamine_earliest /// penicillamine_latest /// sulfasalazine_earliest /// sulfasalazine_latest /// mesalazine_earliest /// mesalazine_latest {

    capture confirm string variable `var'
    if _rc!=0 {
        assert `var'==.
        rename `var' `var'_date
    }

    else {
            replace `var' = `var' + "-15"
            rename `var' `var'_dstr
            replace `var'_dstr = " " if `var'_dstr == "-15"
            gen `var'_date = date(`var'_dstr, "YMD") 
            order `var'_date, after(`var'_dstr)
            drop `var'_dstr
    }

format `var'_date %td

}

/conversion for dates with day already included/

foreach var of varlist icu_date_admitted /// died_date_cpns /// died_date_ons /// first_pos_test_sgss /// first_pos_test_primcare /// {

    capture confirm string variable `var'
    if _rc!=0 {
        assert `var'==.
        rename `var' `var'_date
    }

    else {
            rename `var' `var'_dstr
            gen `var'_date = date(`var'_dstr, "YMD") 
            order `var'_date, after(`var'_dstr)
            drop `var'_dstr
            gen `var'_date15 = `var'_date+15
            order `var'_date15, after(`var'_date)
            drop `var'_date
            rename `var'_date15 `var'_date
    }

format `var'_date %td

}

/ RENAME VARAIBLES===========================================================/

/ CREATE BINARY VARIABLES====================================================/

foreach var of varlist crohns_disease_date /// ulcerative_colitis_date /// ibd_uncla_date /// psoriasis_date /// atopic_dermatitis_date /// hidradenitis_suppurativa_date /// psoriatic_arthritis_date /// rheumatoid_arthritis_date /// ankylosing_spondylitis_date /// chronic_cardiac_disease_date /// hypertension_date /// chronic_respiratory_disease_date /// copd_date /// chronic_liver_disease_date /// stroke_date /// lung_cancer_date /// haem_cancer_date /// other_cancer_date /// diabetes_date /// esrf_date /// creatinine_measured_date /// organ_transplant_date /// bmi_measured_date /// oral_prednisolone_earliest_date /// oral_prednisolone_latest_date /// anti_tnf_earliest_date /// anti_tnf_latest_date /// anti_il6_earliest_date /// anti_il6_latest_date /// anti_il1223_earliest_date /// anti_il1223_latest_date /// anti_il1_earliest_date /// anti_il1_latest_date /// anti_il4_earliest_date /// anti_il4_latest_date /// jak_inhibitors_earliest_date /// jak_inhibitors_latest_date /// rituximab_earliest_date /// rituximab_latest_date /// anti_integrin_earliest_date /// anti_integrin_latest_date /// azathioprine_earliest_date /// azathioprine_latest_date /// ciclosporin_earliest_date /// ciclosporin_latest_date /// gold_earliest_date /// gold_latest_date /// leflunomide_earliest_date /// leflunomide_latest_date /// mercaptopurine_earliest_date /// mercaptopurine_latest_date /// methotrexate_earliest_date /// methotrexate_latest_date /// mycophenolate_earliest_date /// mycophenolate_latest_date /// penicillamine_earliest_date /// penicillamine_latest_date /// sulfasalazine_earliest_date /// sulfasalazine_latest_date /// mesalazine_earliest_date /// mesalazine_latest_date /// icu_admitted_date /// died_cpns_date /// died_ons_date /// first_pos_test_sgss_date /// first_pos_test_primcare_date { / date ranges are applied in python, so presence of date indicates presence of disease in the correct time frame / local newvar = substr("var'", 1, length("var'") - 5) gen newvar' = (var'!=. ) order newvar', after(var') }

/ CREATE VARIABLES===========================================================/

/ DEMOGRAPHICS /

rearrange in order of prevalence recode ethnicity 2=6 / mixed to 6 / recode ethnicity 3=2 / south asian to 2 / recode ethnicity 4=3 / black to 3 / recode ethnicity 6=4 / mixed to 4 */

label define ethnicity 1 "White" /// 2 "South Asian" /// 3 "Black" /// 4 "Mixed" /// 5 "Other" /// .u "Unknown" label values ethnicity ethnicity

gen ethnicity2 = ethnicity replace ethnicity2 = . if ethnicity == .u

/ IMD /

label define imd 1 "1 least deprived" 2 "2" 3 "3" 4 "4" 5 "5 most deprived" .u "Unknown" label values imd imd

/ Age variables / ****works if ages 18 and over

recode age 18/39.9999 = 1 /// 40/49.9999 = 2 /// 50/59.9999 = 3 /// 60/69.9999 = 4 /// 70/79.9999 = 5 /// 80/max = 6, gen(agegroup)

label define agegroup 1 "18-<40" /// 2 "40-<50" /// 3 "50-<60" /// 4 "60-<70" /// 5 "70-<80" /// 6 "80+"

label values agegroup agegroup

/ Body Mass Index /

replace bmi = . if bmi_age < 16 replace bmi = . if bmi_time > 10 & bmi_time != .

gen bmicat = . recode bmicat . = 1 if bmi < 18.5 recode bmicat . = 2 if bmi < 25 recode bmicat . = 3 if bmi < 30 recode bmicat . = 4 if bmi < 35 recode bmicat . = 5 if bmi < 40 recode bmicat . = 6 if bmi < . replace bmicat = .u if bmi >= .

label define bmicat 1 "Underweight (<18.5)" /// 2 "Normal (18.5-24.9)" /// 3 "Overweight (25-29.9)" /// 4 "Obese I (30-34.9)" /// 5 "Obese II (35-39.9)" /// 6 "Obese III (40+)" /// .u "Unknown (.u)"

label values bmicat bmicat

label define obese4cat 1 "No record of obesity" /// 2 "Obese I (30-34.9)" /// 3 "Obese II (35-39.9)" /// 4 "Obese III (40+)"

label values obese4cat obese4cat order obese4cat, after(bmicat)

/ Smoking /

gen smoke = 1 if smoking_status == "N" replace smoke = 2 if smoking_status == "E" replace smoke = 3 if smoking_status == "S" replace smoke = .u if smoking_status == "M" replace smoke = .u if smoking_status == ""

label values smoke smoke drop smoking_status

/ CLINICAL COMORBIDITIES /

/ GP consultation rate / replace gp_consult_count = 0 if gp_consult_count <1

/ eGFR /

replace creatinine = . if creatinine_measured_date == . replace creatinine_measured_date = . if creatinine == .

gen min = . replace min = SCr_adj/0.7 if male==0 replace min = SCr_adj/0.9 if male==1 replace min = min^-0.329 if male==0 replace min = min^-0.411 if male==1 replace min = 1 if min<1

gen max=. replace max=SCr_adj/0.7 if male==0 replace max=SCr_adj/0.9 if male==1 replace max=max^-1.209 replace max=1 if max>1

gen egfr=minmax141 replace egfr=egfr(0.993^age) replace egfr=egfr1.018 if male==0 label var egfr "egfr calculated using CKD-EPI formula with no eth"

/ 0 "No CKD, eGFR>60" or missing -- have been shown reasonable in CPRD 2 "stage 3a, eGFR 45-59" 3 "stage 3b, eGFR 30-44" 4 "stage 4, eGFR 15-29" 5 "stage 5, eGFR <15" /

gen egfr_cat = . recode egfr_cat . = 3 if egfr < 30 recode egfr_cat . = 2 if egfr < 60 recode egfr_cat . = 1 if egfr < . replace egfr_cat = .u if egfr >= .

label define egfr_cat 1 ">=60" /// 2 "30-59" /// 3 "<30" /// .u "Unknown (.u)"

label values egfr_cat egfr_cat

*if missing eGFR, assume normal

gen egfr_cat_nomiss = egfr_cat replace egfr_cat_nomiss = 1 if egfr_cat == .u

label define egfr_cat_nomiss 1 ">=60/missing" /// 2 "30-59" /// 3 "<30" label values egfr_cat_nomiss egfr_cat_nomiss

gen egfr_date = creatinine_measured_date format egfr_date %td

label define ckd 0 "No CKD" 1 "CKD" label values ckd ckd label var ckd "CKD stage calc without eth"

/ HbA1c /

/ Diabetes severity /

/ Express HbA1c as percentage /

/ Categorise hba1c and diabetes /

label define diabcat 1 "No diabetes" /// 2 "Controlled diabetes" /// 3 "Uncontrolled diabetes" /// 4 "Diabetes, no hba1c measure" label values diabcat diabcat

*creat other comorbid variables gen combined_cv_comorbid =1 if chronic_cardiac_disease ==1 | stroke==1

/ POPULATIONS =============================================================/

/ Diagnosis =============/ include only most recent diagnosis within each specialty Rheum replace rheumatoid_arthritis =0 if psoriatic_arthritis_date > rheumatoid_arthritis_date & psoriatic_arthritis_date !=. replace psoriatic_arthritis =0 if rheumatoid_arthritis_date > psoriatic_arthritis_date & rheumatoid_arthritis_date !=. replace ankylosing_spondylitis =0 if ankylosing_spondylitis_date > ankylosing_spondylitis_date & ankylosing_spondylitis_date !=. Derm replace psoriasis =0 if hidradenitis_suppurativa_date > psoriasis_date & hidradenitis_suppurativa_date !=. replace psoriasis =0 if atopic_dermatitis_date > psoriasis_date & atopic_dermatitis_date !=. replace hidradenitis_suppurativa =0 if psoriasis_date > hidradenitis_suppurativa_date & psoriasis_date !=. replace hidradenitis_suppurativa =0 if atopic_dermatitis_date > hidradenitis_suppurativa_date & atopic_dermatitis_date !=. replace atopic_dermatitis =0 if psoriasis_date > atopic_dermatitis_date & psoriasis_date !=. replace atopic_dermatitis =0 if hidradenitis_suppurativa_date > atopic_dermatitis_date & hidradenitis_suppurativa_date !=. Gastro replace ibd_uncla =0 if ulcerative_colitis_date > ibd_uncla_date & ulcerative_colitis_date !=. replace ibd_uncla =0 if crohns_disease_date > ibd_uncla_date & crohns_disease_date !=. replace ulcerative_colitis =0 if crohns_disease_date > ulcerative_colitis_date & crohns_disease_date !=. replace ulcerative_colitis =0 if ibd_uncla_date > ulcerative_colitis_date & ibd_uncla_date !=. replace crohns_disease =0 if ulcerative_colitis_date > crohns_disease_date & ulcerative_colitis_date !=. replace crohns_disease =0 if ibd_uncla_date > crohns_disease_date & ibd_uncla_date !=.

consider the effect of patients diagnosed with imid post 1st March 2020 ignoring this will bias to null *diagnoses after 1st March have been culled via python code

gen imid = . replace imid = 1 if rheumatoid_arthritis ==1 | psoriatic_arthritis ==1 | ankylosing_spondylitis==1 | ibd_uncla ==1 | ulcerative_colitis ==1 | crohns_disease ==1 | psoriasis ==1 | hidradenitis_suppurativa ==1 replace imid = 0 if rheumatoid_arthritis !=1 & psoriatic_arthritis !=1 & ibd_uncla !=1 & ulcerative_colitis !=1 & crohns_disease !=1 & psoriasis !=1 & hidradenitis_suppurativa !=1 & ankylosing_spondylitis !=1

label define imid 0 "Gen Pop" 1 "IMID" label values imid imid

*gen adj covariate, imid type

gen imidtype =1 if ulcerative_colitis ==1 recode imidtype .=1 if crohns_disease ==1 recode imidtype .=1 if ibd_uncla ==1 recode imidtype .=2 if rheumatoid_arthritis ==1 recode imidtype .=2 if psoriatic_arthritis ==1 recode imidtype .=2 if ankylosing_spondylitis ==1 recode imidtype .=3 if psoriasis ==1 recode imidtype .=3 if hidradenitis_suppurativa ==1 recode imidtype .=3 if atopic_dermatitis ==1

label define imidtype 1"Bowel" 2"Joint" 3"Skin" label values imidtype imidtype

gen genbowel =1 if imidtype ==1 replace genbowel =0 if imid ==0 label define genbowel 0"Gen Pop" 1"Bowel" label values genbowel genbowel

gen genjoint =1 if imidtype ==2 replace genjoint =0 if imid ==0 label define genjoint 0"Gen Pop" 1"Joint" label values genjoint genjoint

gen genskin =1 if imidtype ==3 replace genskin =0 if imid ==0 label define genskin 0"Gen Pop" 1"Skin" label values genskin genskin

gen bowel =0 replace bowel =1 if crohns_disease ==1 | ibd_uncla ==1 | ulcerative_colitis ==1

gen skin =0 replace skin =1 if psoriasis ==1 | hidradenitis_suppurativa ==1

gen joint =0 replace joint =1 if rheumatoid_arthritis ==1 | psoriatic_arthritis ==1 | ankylosing_spondylitis ==1

label define imid_detailed 1"Ulcerative colitis"

*Loop to replace missing with 0 foreach var of varlist oral_prednisolone_3m_0m /// oral_prednisolone_6m_3m /// oral_prednisolone_12m_6m ///
anti_tnf_3m_0m /// anti_tnf_6m_3m /// anti_tnf_12m_6m /// anti_il6_3m_0m /// anti_il6_6m_3m /// anti_il6_12m_6m /// anti_il1223_3m_0m /// anti_il1223_6m_3m /// anti_il1223_12m_6m /// anti_il1_3m_0m /// anti_il1_6m_3m /// anti_il1_12m_6m /// anti_il4_3m_0m /// anti_il4_6m_3m /// anti_il4_12m_6m /// jak_inhibitors_3m_0m /// jak_inhibitors_6m_3m /// jak_inhibitors_12m_6m /// rituximab_3m_0m /// rituximab_6m_3m /// rituximab_12m_6m /// anti_integrin_3m_0m /// anti_integrin_6m_3m /// anti_integrin_12m_6m /// azathioprine_3m_0m /// azathioprine_6m_3m /// azathioprine_12m_6m /// ciclosporin_3m_0m /// ciclosporin_6m_3m /// ciclosporin_12m_6m /// gold_3m_0m /// gold_6m_3m /// gold_12m_6m /// leflunomide_3m_0m /// leflunomide_6m_3m /// leflunomide_12m_6m /// mercaptopurine_3m_0m /// mercaptopurine_6m_3m /// mercaptopurine_12m_6m /// methotrexate_3m_0m /// methotrexate_6m_3m /// methotrexate_12m_6m /// mycophenolate_3m_0m /// mycophenolate_6m_3m /// mycophenolate_12m_6m /// penicillamine_3m_0m /// penicillamine_6m_3m /// penicillamine_12m_6m /// sulfasalazine_3m_0m /// sulfasalazine_6m_3m /// sulfasalazine_12m_6m /// mesalazine_3m_0m /// mesalazine_6m_3m /// mesalazine_12m_6m {

                    replace `var' =0 if `var' ==.
                    }

*Define those that started > or < 6 months prior to index date

label define commence 0"Within last 6 months" /// 1"More than 6 months ago"

foreach var of varlist anti_tnf_earliest_date /// anti_il1223_earliest_date /// jak_inhibitors_earliest_date {

            gen `var'_com = 1 if `var'+180 < (date("$indexdate", "DMY"))
            recode `var'_com .=0 if `var' !=.
            label values `var'_com commence
            order `var'_com, after(`var')                   
                    }

*stand sys drugs data are count, not binary! gen standsys =1 if azathioprine_3m_0m >=1 | azathioprine_6m_3m >=1 | ciclosporin_3m_0m >=1 |ciclosporin_6m_3m >=1 | leflunomide_3m_0m >=1 |leflunomide_6m_3m >=1 | mercaptopurine_3m_0m >=1 |mercaptopurine_6m_3m >=1 | methotrexate_3m_0m >=1 | methotrexate_6m_3m >=1 | mycophenolate_3m_0m >=1 | mycophenolate_6m_3m >=1 | sulfasalazine_3m_0m >=1 |sulfasalazine_6m_3m >=1 | mesalazine_3m_0m >=1 | mesalazine_6m_3m >=1 replace standsys =. if imid !=1

gen standsys3m =1 if azathioprine_3m_0m >=1 | ciclosporin_3m_0m >=1 | leflunomide_3m_0m >=1 | mercaptopurine_3m_0m >=1 | methotrexate_3m_0m >=1 | mycophenolate_3m_0m >=1 | sulfasalazine_3m_0m >=1 | mesalazine_3m_0m >=1 replace standsys3m =. if imid !=1

gen tnf =1 if anti_tnf_6m_3m !=0 | anti_tnf_3m_0m !=0 replace tnf =. if imid !=1

gen tnfmono =1 if tnf==1 & standsys !=1 recode tnfmono .=0 if tnf==1 & standsys ==1

label define tnfmono 0 "TNF combination" /// 1 "TNF monotherapy" label values tnfmono tnfmono label var tnfmono "TNF strategy"

*high cost drug data pull through as binary variable, not count gen standtnf =1 if tnf ==1 replace standtnf =0 if standsys ==1 & tnf !=1

gen standtnf3m =1 if anti_tnf_3m_0m ==1 replace standtnf3m =0 if anti_tnf_3m_0m !=1 & standsys3m ==1

gen il12_23 =1 if anti_il1223_3m_0m !=0 | anti_il1223_6m_3m !=0 replace il12_23 =. if imid !=1

gen standil1223 =1 if il12_23 ==1 replace standil1223 =0 if standsys ==1 & il12_23 !=1

gen standil1223_3m =1 if anti_il1223_3m_0m ==1 replace standil1223_3m =0 if anti_il1223_3m_0m !=1 & standsys3m ==1

gen jaki =1 if jak_inhibitors_3m_0m !=0 | jak_inhibitors_6m_3m !=0 replace jaki =. if imid !=1

gen standjaki =1 if jaki ==1 replace standjaki =0 if standsys ==1 & jaki !=1

gen standjaki3m =1 if jak_inhibitors_3m_0m ==1 replace standjaki3m =0 if jak_inhibitors_3m_0m !=1 & standsys3m ==1

gen ritux =1 if rituximab_3m_0m !=0 | rituximab_6m_3m !=0 | rituximab_12m_6m !=0 replace ritux =. if rheumatoid_arthritis !=1

gen standritux =1 if ritux ==1 replace standritux =0 if standsys ==1 & ritux !=1

gen standritux3m =1 if rituximab_3m_0m ==1 replace standritux3m =0 if rituximab_3m_0m !=1 & standsys3m ==1

gen il6 =1 if anti_il6_3m_0m !=0 | anti_il6_6m_3m !=0 replace il6 =. if rheumatoid_arthritis !=1

gen standil6 =1 if il6 ==1 replace standil6 =0 if standsys ==1 & il6 !=1

gen standil63m =1 if anti_il6_3m_0m ==1 replace standil63m =0 if anti_il6_3m_0m !=1 & standsys3m ==1

gen mesalazine =1 if mesalazine_3m_0m >=1 | mesalazine_6m_3m >=1 replace mesalazine =. if imid !=1

gen standmesalazine =1 if mesalazine >=1 replace standmesalazine =0 if standsys ==1 & mesalazine ==0

gen standmesalazine3m =1 if mesalazine_3m_0m >=1 replace standmesalazine3m =0 if mesalazine_3m_0m ==0 & standsys3m ==1

gen steroidcat = 0 recode steroidcat =1 if oral_prednisolone_3m_0m >=1 & oral_prednisolone_3m_0m!=.

gen imiddrugcategory = (standard v highcost) gen imiddrugcatdetail = (standard v high cost drug subgroupings)

/ OUTCOME AND SURVIVAL TIME==================================================/ / Cohort entry and censor dates /

/ Outcomes /

*date of COVID ITU admission ** issue we have is how we define an ITU admission as a COVID one. gen icu_admit_diff = icu_admitted_date - first_pos_test_sgss_date replace icu_admit_diff =. if icu_admit_diff <-5 gen icu_admit_date_covid = icu_admitted_date if icu_admit_diff <28

gen icu_or_death_covid_date = icu_admit_date_covid replace icu_or_death_covid_date = died_ons_date_covid if icu_admit_date_covid ==. gen icu_or_death_covid =1 if icu_or_death_covid_date !=.

format died_ons_date_covid died_ons_date_noncovid icu_admit_date_covid icu_or_death_covid_date %td

*Variables needed from Python: first_pos_test_sgss, mesalazine, AxSPA, AD, LOS (check resp excludes asthma)

/ CENSORING / / SET FU DATES===============================================================/

/Tables=====================================================================================/ Table 1a - need to create grouping variable for diagnoses- wait for all diagnostic covariates. table1_mc, by(imid) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table1a") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f ) not pulling flu vaccine status (originally in protocol)

Table 1b - by imid type table1_mc, by(imidtype) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table1b") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f ) / *Table 1c - by imid type allowing contribution to multiple groups - expand groups table1_mc, by(imidtype) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table1c") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f )

Table 1d - by imid type detailed - allow multiple group contribution table1_mc, by(imiddetailed) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table1d") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f ) /

*Table 2a - high cost drugs (v non-high cost) - single group contribution only table1_mc, by(imiddrugcategory) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table2a") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f )

*Table 2b - high cost drugs (detailed) - single group contribution only table1_mc, by(imiddrugcatdetail) total(before) onecol iqrmiddle(",") saving("$tables.xlsx", sheet("Table2b") cell(A1) sheetmodify keepcellfmt) /// vars(agegroup cat %5.1f \ /// sex bin %5.1f \ /// bmicat cat %5.1f \ /// obese4cat cat %5.1f \ /// ethnicity cat %5.1f \ /// imd cat %5.1f \ /// smoke cat %5.1f \ /// chronic_cardiac_disease bin %5.1f \ /// stroke bin %5.1f \ /// combined_cv_comorbid bin %5.1f \ /// hypertension bin %5.1f \ /// diabcat cat %5.1f \ /// ckd_egfr cat %5.1f \ /// esrf bin %5.1f \ /// gp_consult_count contn %5.1f \ /// steroidcat bin %5.1f \ /// oral_prednisolone_3m_0m contn %5.1f )

/Primary objective 1========================================================================/ *generate censor date egen stop = min(died_ons_date, mdy(10,01,2020))

stset died_ons_date, id(patient_id) failure(died_ons_covid_flag_any==1) origin(time enter_date) scale(365.25) /// exit(died_ons_covid_flag_any==1 time stop)

strate imid, per(1000) output(imid, replace)

asdoc stcox imid i.agegroup male, save(outputs) title(primaryobjective1unadj) replace sts graph, by(imid) xtitle("Analysis time (years)") saving(primeob1_nonadj, replace) graph export "primeob1_nonadj.svg", as(svg) replace

*graph schoenfeld residuals - to be added here

asdoc stcox imid i.agegroup male, save(outputs) title(primaryobjective1limitedadjusted) append

asdoc stcox imid i.agegroup male i.ethnicity2 i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusted_completecaseethnicity) append

asdoc stcox imid i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer stroke i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusted) append

asdoc stcox imid i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease cancer stroke i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusted_noethnicity) append

/Primary objective 1- Sensitivity analysis 1 ===========================/ asdoc stcox imid i.agegroup male i.ethnicity i.imd bmicat bowel skin joint chronic_cardiac_disease cancer i.diabcat steroidcat if gp_consult ==1, save(outputs) title(primaryobjective1sensitivity1) append sts graph if gp_consult ==1, by(imid) xtitle("Analysis time (years)") saving(primeob1sens1, replace) graph export "primeob1sens1.svg", as(svg) replace

/Primary objective 1- Sensitivity analysis 2 ===========================/ asdoc stcox imid i.agegroup male i.ethnicity i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat i.ckd chronic_liver_disease chronic_respiratory_disease, save(outputs) title(primaryobjective1sensitivity2) append

/Primary objective 1 Using death or ITU========================================================================/ egen stopicu = min(icu_or_death_covid_date, mdy(10,01,2020))

stset icu_or_death_covid_date, id(patient_id) failure(icu_or_death_covid==1) origin(time enter_date) scale(365.25) /// exit(icu_or_death_covid==1 time stop)

strate imid, per(1000) output(imid, replace) asdoc stcox imid i.agegroup male, save(outputs) title(primaryobjective1limitedadjitudeath) replace

sts graph, by(imid) xtitle("Analysis time (years)") saving(primeob1_nonadjitudeath, replace) graph export "primeob1_nonadj.svg", as(svg) replace

asdoc stcox imid i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusteditudeath) append

asdoc stcox imid i.agegroup male i.imd i.ethnicity2 bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusteditudeath_ethnicity) append

asdoc stcox imid i.agegroup male i.imd i.ethnicity bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective1adjusteditudeath_ethnicity_nomiss) append

/Primary objective 2========================================================================/ stset died_ons_date, id(patient_id) failure(died_ons_covid_flag_any==1) origin(time enter_date) scale(365.25) /// exit(died_ons_covid_flag_any==1 time stop)

*2a: TNF vs standard systemics

strate standtnf, per(1000) output(standtnf,replace)

asdoc stcox standtnf, save(outputs) title(primaryobjective2aunadj) append

sts graph, by(standtnf) xtitle("Analysis time (years)") saving(primeob2a, replace) graph export "primeob2a.svg", as(svg) replace

asdoc stcox standtnf i.agegroup male, save(outputs) title(primaryobjective2limitedadj) append

asdoc stcox standtnf i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective2aadjusted) append

*include ICU in composite now for 2a

stset icu_or_death_covid_date, id(patient_id) failure(icu_or_death_covid==1) origin(time enter_date) scale(365.25) /// exit(icu_or_death_covid==1 time stop)

strate standtnf, per(1000) output(standtnf,replace) asdoc stcox standtnf, save(outputs) title(primaryobjective2aunadj_inc_icu) append

sts graph, by(standtnf) xtitle("Analysis time (years)") saving(primeob2a_inc_icu, replace) graph export "primeob2a.svg", as(svg) replace

asdoc stcox standtnf i.agegroup male, save(outputs) title(primaryobjective2limitedadj_inc_icu) append

asdoc stcox standtnf i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective2aadjusted_inc_icu) append

*2a sensitivity 1: TNF combo v monotherapy (keep to just death or icu) asdoc stcox tnfmono i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective2asensitivity1) append

*2a sensitivity 2: exclude GP non attenders asdoc stcox standtnf i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat if gp_consult ==1, save(outputs) title(primaryobjective2asensitivity2) append

*2a sensitivity 3: Additional confounders asdoc stcox standtnf i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat i.ckd chronic_liver_disease chronic_respiratory_disease, /// save(outputs) title(primaryobjective2asensitivity3) append

*2a sensitivity 4: restricted exposure window asdoc stcox standtnf3m i.agegroup male i.imd bmicat bowel skin joint chronic_cardiac_disease stroke cancer i.diabcat steroidcat, save(outputs) title(primaryobjective2asensitivity4) append

*2a sensitivity 5: exclusion of infliximab- not available in dataset currently.

/ 2a sensitivity 6: covid positivity- ?include primary care swabs or just sgss? stset first_pos_test_sgss_date, id(patient_id) failure(first_pos_test_sgss==1) origin(time enter_date) scale(365.25) exit(first_pos_test_sgss==1 time mdy(10,01,2020)) asdoc stcox standtnf i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m, save(outputs) title(primaryobjective2asensitivity6) append */

*2b: IL12_23 vs standard systemics

asdoc stcox standil1223, save(outputs) title(primaryobjective2bunadj) append sts graph, by(standil1223) xtitle("Analysis time (years)") saving(primeob2b, replace) graph export "primeob2b.svg", as(svg) replace asdoc stcox standil1223 i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m, save(outputs) title(primaryobjective2badjusted) append

*2b sensitivity 1: exclude GP non attenders asdoc stcox standil1223 i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m if gp_consult ==1, save(outputs) title(primaryobjective2bsensitivity1) append

*2b sensitivity 2: Additional confounders asdoc stcox standil1223 i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m ckd chronic_liver_disease chronic_respiratory_disease, /// save(outputs) title(primaryobjective2bsensitivity2) append

*2b sensitivity 3: restricted exposure window asdoc stcox standil12233m i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m , save(outputs) title(primaryobjective2bsensitivity3) append

*2b sensitivity 4: covid positivity- ?include primary care swabs or just sgss?
stset first_pos_test_sgss_date, id(patient_id) failure(first_pos_test_sgss==1) origin(time enter_date) scale(365.25) exit(first_pos_test_sgss==1 time mdy(10,01,2020)) asdoc stcox standil1223 i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m, save(outputs) title(primaryobjective2bsensitivity4) append

*2c: Il17 vs standard systemics (Psoriasis, PsA and AxSpa only) - need AS and il17 variable to complete

*2d: Jaki vs standard systemics

asdoc stcox standjaki, save(outputs) title(primaryobjective2dunadj) append sts graph, by(standjaki) xtitle("Analysis time (years)") saving(primeob2d, replace) graph export "primeob2d.svg", as(svg) replace asdoc stcox standjaki i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m, save(outputs) title(primaryobjective2dadjusted) append

*2d sensitivity 1: exclude GP non attenders asdoc stcox standjaki i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m if gp_consult ==1, save(outputs) title(primaryobjective2dsensitivity1) append

*2d sensitivity 2: Additional confounders asdoc stcox standjaki i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m ckd chronic_liver_disease chronic_respiratory_disease, /// save(outputs) title(primaryobjective2dsensitivity2) append

*2d sensitivity 3: restricted exposure window asdoc stcox standjaki3m i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m , save(outputs) title(primaryobjective2dsensitivity3) append

*2d sensitivity 4: covid positivity- ?include primary care swabs or just sgss? stset first_pos_test_sgss_date, id(patient_id) failure(first_pos_test_sgss==1) origin(time enter_date) scale(365.25) exit(first_pos_test_sgss==1 time mdy(10,01,2020)) asdoc stcox standjaki i.agegroup male i.ethnicity i.imd bmicat i.imidtype chronic_cardiac_disease cancer i.diabcat oral_prednisolone_3m_0m, save(outputs) title(primaryobjective2dsensitivity4) append

NikNakk commented 3 years ago

This code is include in #24