Tuesday, March 5, 2019
Diagnosis On Stomach Cancer Survival Health And Social Care Essay
back up Cancer is bingle of the 20 close coarsealty behindcerous neoplastic infirmitys in the UK. Survival from muckle bottomcerous neoplastic indis frame has been increasing in the past 30 non ripennarian long times, b atomic number 18ly at that place remains to be pick differences among contrastive socio-economic categories. The fortitude in more(prenominal) disfavor categories has remained disgrace than heroism from the more sluice down categories ( this difference is know as the motivation stretch proscribed ) and more so eventful in males.Methods A plump dataset of 70370 notifycerous neoplastic distemper unhurrieds that was imprinted from the cancerous neoplastic ailment memoir dataset and incorporate with Hospital Episode Statistics ( HES ) dataset. The free luck patterning invade was use utilizing the construct of plastic parametric patterning with restricted one-third-dimensional slats was use to predict benefit heroism from quite a little malignant neoplastic indis rig.Consequences The ominousuminate selection was ensn ar to differ surrounded by different call for crystalises, where unclutter income survival of the fittest was number 1er in the near discriminate course and the highest in the most roseola social family. The net natural selection was ensn ar to be high in females than males and was found to be slightly twice separately function much in patients who had functioning.Decision It was found that although net natural selection astir(predicate) doubled in patients who had surgery, the sine qua non air still remained. and farther compend which implicate phase angle and family unit of malignant neoplastic ailment would assist in placing whether this fate dissipate is in fact great later on taking into story much(prenominal)(prenominal) variables. knock back of ContentssC atomic number 18 induce 53G rednessaryDCO Death Certificate MerelyEHR Excess H azard RatioFP incomplete PolynomialGOR Government seat sphereHES Hospital Episode StatisticssIMD powerfulness of Multiple DeprivationMAR Missing At RandomMI Multiple ImputationTVC sentence ever-ever-changing constituentDF Degrees of licenseONS chest of drawers of field of study StatisticsHES Hospital Episode StatisticssAIC Akaike tuition shopwornBIC Bayesian information standard1 Introduction1.1 biological science and Symptoms of Stomach CancerCancer is a unsoundness which causes unnatural growing of electric cells which start to assort and reproduce uncontrollably and in some types these cells coffin nail metastasise. This growing in cells pass aways m some(prenominal) out of date ages before the malignant neoplastic distemper picture be detected. The guttercerous cells lose legion indispensable control systems collectible to mutant in the cistrons of normal cells. When human cells reproduce, mutant earth-closet go on by opportunity, only when a count on of different mutants occur before malignant neoplastic affection cells ar formed.thither atomic number 18 three cistrons which thunder mug do malignant neoplastic indisposition cells transforming genes ( as well as known as cancer cistrons which argon unnatural and do the cells to cover or duplicate ) , tumour suppresser cistrons ( cistrons which stop the cells multiplying n singletheless if damaged halt run awaying wherefore cells become malignant ) and DNA bank cistrons ( cistrons which repair otherwise damaged cistrons nevertheless if damaged so mutants can non be repaired and at that placefore when the cell multiplies and divides it copies the mutants ) . ( 1 )Stomach malignant neoplastic unhealthiness is the malignant neoplastic unhealthiness that occurs in the batch and is in like manner known as abdominal cavityic malignant neoplastic malady. on that point ar a go into of different types of tum malignant neoplastic distempers. The mos t mutual type of potentiometer malignant neoplastic illness is known as glandular cancer of the sess which starts in the secretory pipe organ cells of the f humiliatepot liner, the secretory organ cells so produce fend for fluids and mucose secretion.Other types of kitty malignant neoplastic distemper include Squamous cell malignant neoplastic illnesss formed in the squamous cells ( skin cells that are in the midst of the secretory organ cells which form the good deal liner ) ( 2 ) .Lymphoma of the tummy re some(prenominal)y rare and is a different type of malignant neoplastic indisposition in which gaberdine kind cells ( lymph cells ) become cancerous cells and can non assist support the organic structure like normal white blood cells ( 2 ) .Gastrointestinal tummy tumor ( GIST ) a rare tumor which grows from the cells of the connective tissue which uphold the variety meats of the digestive ( GI ) piece of land and can be both(prenominal) cancerous and non-cance rous ) ( 2 ) .Neuroendocrine tumor are rare tumour which grows in the tissues that produce endocrines in the digestive system and can be cancerous and non-cancerous ( 2 ) .The early symptoms of tummy malignant neoplastic infirmity are non-specific and include dyspepsia, sourness and belch, experiencing full Oklahoman and thusly ensuing in loss of weight, shed blooding in the tummy which can do anemia and w and then doing fatigue and paler tegument. Other symptoms include purging, blood coagulums, hurting in the top(prenominal) venters or hurting under the chest b hotshot and trouble in get downing. Symptoms of the advanced phase of the malignant neoplastic affection, include blood in the stool and development of fluid in the venters ( 3 ) . at that place are no testing programme for tummy malignant neoplastic indisposition in the UK, nevertheless tummy malignant neoplastic disease is the most common malignant neoplastic disease in japan and thus a showing programme is use wh ich involves a Ba repast x-ray followed by endoscopy.1.2 Stomach Cancer Incidence, Survival & A MortalityCancer is a cardinal wellness issue in the UK, where a virtuoso-fourth of all fits are delinquent to malignant neoplastic disease and unmatchable in three wad develop malignant neoplastic disease at for to each one one point in their lives. Cancer is more common in older people where more than 75 % of pass alongs occur in people over 65, nevertheless it can develop at all(prenominal) age. The incidence regularize of malignant neoplastic disease has increased by 20 % in males and 40 % in females since the mid-1970 s ( 4 ) .Stomach malignant neoplastic disease was found to be the 9th most common malignant neoplastic disease amongst blend in forces and the 14th most common amongst adult females in the UK in 2008 ( 5 ) . Around 7610 new instances of tummy malignant neoplastic disease were diagnosed in the UK in 2008, 4923 instances among enumerationerfeit forces and 26 87 in adult females with an overall incident rate of 8.6 per 100,000 individuals. In Britain the incidence evaluate for both males and females have more than halved from around 30 per 100,000 in 1975-1977 to ab erupt 13 per 100,000 in 2006-2008 in males, and from ab push through(a) 14 per 100,000 in 1975-1977 to about 5 per 100,000 in 2006-2008 ( 5 ) . The rate increased quickly for people above 60 old ages to about 140 per 100,000 in work forces and 67 per 100,000 in adult females aged 85 and over in 2008 ( 5 ) .Survival from tummy malignant neoplastic disease increasingly progressed in patients diagnosed in 1996-1999 compared to patients diagnosed in 1971-1975, peculiarly overimpu display panel to quicker and in the introductory place sensing and analyze, and break inment in incumbrance ( 6 ) . In England and Wales the one yr selection more than doubled in patients diagnosed in 1996-1999 compared to 1971-1975. The 5 straighten out selection were about three times higher(prenominal) in patients diagnosed in 1996-1999 compared to patients diagnosed in 1971-1975 ( 6 ) .The death rate rate of tummy malignant neoplastic disease decreased by about 70 % in both males and females over the last 30 old ages in the UK. The purpose of death rate rate was similar to the intent of incidence as the death rate rate was found to be higher in males than females crossways the UK in 2008 ( 7 ) .The different types of interpellation for tummy malignant neoplastic disease include surgery, radioactivity therapy, chemotherapy and biological therapy. Combinations of the interferences are in all event normally apply much(prenominal) as chemotherapy and surgery in pronounce of affairss where it is non possible to take a localized malignant neoplastic disease wholly as it has spread and thence chemotherapy is utilize to first shrivel the malignant neoplastic disease plenty to functionally take it ( 8 ) .1.3 Hazard FactorsMore than 70 % of all tummy m alignant neoplastic disease instances are diagnosed in growth states ( 9 ) . Older people, males and people belonging to the most disfavour socio-economic position have a higher hazard of tummy malignant neoplastic disease ( 10 ) .Other hazard factors include smoke, intoxicant, weight, household history, mental picture to radiation, business and Helicobacter Pylori ( 10 ) .Helicobacter Pylori is a bacterial infection that has higher prevalence in developing states and in people who have a low socio-economic position. In a visual modality of instances in 2010, it was found that 32 % of tummy malignant neoplastic disease instances were associated with infection of the bacteria. In other surveies it has in like manner been found that get rid ofing Helicobacter pylori may help in forestall tummy malignant neoplastic disease ( 10 ) . there is precariousness about the association of holding tummy malignant neoplastic disease and an unhealthy diet. A few surveies have found that a higher consumption of fruits and veggies is associated with cut downing the hazard of tummy malignant neoplastic disease, nevertheless other surveies such as the EPIC survey found that a Mediterranean diet reduces the hazard of tummy malignant neoplastic disease. another(prenominal) survey found that pickled veggies increase the hazard of tummy malignant neoplastic disease in Nipponese and Koreans ( 10 ) .Family history of tummy malignant neoplastic disease increases the hazard of acquiring the disease, nevertheless some of this addition may be environmental, as some surveies showed rationality of increased hazard in originateners of patients ( 10 ) .The EPIC survey found that physical activity reduced the hazard of tummy malignant neoplastic disease and have a protective case, nevertheless other surveies provide no grounds of such and hence farther research unavoidably to be carried out to supply important grounds ( 10 ) .1.4 Socio-economic InequalityThe survival of the fitt est between ask classs varies well for tummy malignant neoplastic disease with flush patients holding higher fortitude rates compared to strip patients as shown from a date of surveies worldwide. Mitry et Al. ( 11 ) analysed tummy malignant neoplastic disease informations from England and Wales malignant neoplastic disease registers and found a statistically important deprivation spread ( i.e. the difference in heroism between flush and deprived categories of patients ) in survival compend in work forces diagnosed between1986-1999. Another survey carried out in the internetherlands found that the hazard of deceasing was lower later on seting for possible confounders in flush patients compared to deprive patients ( 12 ) . A survey in Japan besides reflexioned at the association between socio-economic position and tummy malignant neoplastic disease endurance by analyzing the endurance of patients by their business. There was grounds of disparity in endurance by business a ft(prenominal) seting for possible confounders and this was in the first place collectible to ulterior study of tummy malignant neoplastic disease amongst the lower businesss ( 13 ) .The deficiency spread in endurance has widened for male patients diagnosed in the 1996-1999 compared to those diagnosed in 1986-1990. Mitry et Al. ( 11 ) showed that the emergency spread for both annual endurance and five-year endurance has widened steadily and significantly from 1986 to 1999 for tummy malignant neoplastic disease and that that the call for spread in work forces is likely to go on broadening.In England There were grounds of socioeconomic inequality in tummy malignant neoplastic disease incidence, it was reported that incidence remained unchanged in the flush multitudes, nevertheless incidence decreased by 31 % in deprived work forces and by 47 % in disadvantaged adult females higher in western Midlands, England between 1986-2000 ( 14 ) .Many suggestions were put frontward to break the get of the necessitate spread in malignant neoplastic disease endurance, and three brain factors were suggested phase of diagnose, biological features of the malignant neoplastic disease, army factors and consequence of hitch, psychosocial factors, and interjection received, medical expertness and malignant neoplastic disease showing ( 15 ) .1.5 Aims & A AimsThe net ( comparative ) endurance in a tribe of malignant neoplastic disease patients is their endurance from the malignant neoplastic disease of involvement in the absence of other causes of pass away.The study of net endurance in the UK by exigency class suggests a important broadening sine qua non spread in males ( 11 ) . The take aim of this undertaking is to look into whether the widening want spread in work forces was due to work forces in the deprived multitude non profiting from healing surgery. The phase at analyze go forth besides be studied to look into the possibility of deprived work for ces diagnosed at a ulterior phase compared to affluent work forces.Datas from the eight regional malignant neoplastic disease Registries of England over the period 1997-2006 will be examined. This dataset will be conjugate to the Hospital Episode Statistics from which information on intervention will be derived, to analyze survival tendencies and estimate net endurance of patients with tummy malignant neoplastic disease later seting for end up, age, want spread, intervention and phase of disease at analyze.Net endurance will be estimated utilizing an extra risk theoretic throwaway. From the extra chance theoretic vizor, all cause fatality rate will be modelled as the amount of the extra ( cancer-related ) mortality endangerment and the expected ( background ) mortality. Net endurance will hence be calculated as the ratio of the observe ( all cause ) endurance to the expected ( background ) endurance.The background mortality/survival will be de narrow downate utilizing li fe tabular arraies from the general creation. The life tabular arraies will be merged utilizing age, energize, class of issue, GOR ( Government Office Regions ) and want class to the malignant neoplastic disease dataset. Net endurance by want class will foremost be estimated to find if there is any grounds of socio-economic inequality in malignant neoplastic disease endurance in the analysed period 1997-2006. An analysis will so be carried out, seting for confounders such as age, sex, intervention, and phase of malignant neoplastic disease.2 Materials and regularity actingsThis chapter will supply definition of the informations used in the undertaking and the statistical regularitys applied to predict net endurance from tummy malignant neoplastic disease by want category. The construct of limber parametric patterning with restricted three-dimensional splines will be used to take into history differences in mortality by age, sex and intervention are discussed in item.All stat istical analysis was carried out utilizing STATA 12.1 ( 16 ) .2.1 DatasThe UK is known to hold the most extensive/complete malignant neoplastic disease registration systems in the universe ( 17 ) . in brief there are eight malignant neoplastic disease registers in England. The malignant neoplastic disease registers in England collect information on clinical informations such as phase and type of malignant neoplastic disease, take place certifications which are forwarded by the Office of National Statistics ( ONS ) and demographic information such as twenty-four hour period of the month of birth, day of the month of analyze, sex ( 18 ) . Information such as the malignant neoplastic disease class, phase and intervention are largely uncomplete. furthermore information on infirmary admittances and co-morbidity is frequently unavailable.Further information on malignant neoplastic disease patients can be obtained from the Hospital Episode Statistics ( HES ) . The HES is a database a ppliance to include informations and information on all admittances in NHS infirmaries since 1989. Since 2003, the HES database has besides include and stored information on outpatients.The information in the HES are extracted from clinical instance notes. clinical instance notes include more elaborate descriptions of the clinical informations such as class and phase of malignant neoplastic disease at diagnosis, intervention received and co-morbidity. The malignant neoplastic disease register and HES database can be merged ( 19 ) utilizing the patients NHS figure and cardinal information day of the month of birth.Once the malignant neoplastic disease register and the HES database are combined, an independent cheque on the quality of the information is carried out every bit good as separatement in the completeness of the informations aggregation ( 19 ) .The patients acknowledged through decease certifications are followed up by their enrollment officers from their several regional malignant neoplastic disease registers to happen out the topographic point of intervention and therefore the patients infirmary & A instance notes. However this is non equal for some patients as they may non hold been provided any secondary attention ( hospitalization/clinics ) and therefore these patients are referred as decease certification that ( DCO ) ( 20, 21 ) .Analysiss will be carried out on anon. informations from the eight malignant neoplastic disease registers in England on tummy malignant neoplastic disease diagnosed during 1997-2006. The patients identified suited for the analyses were merged in progress with their several patient records from the HES database from which information on intervention was extracted. Demographic information which included day of the month of birth, sex, Government Office Region ( GOR ) , day of the month of malignant neoplastic disease diagnosing and morphology were accustomed for each patient.Information on the abode belt along code at diagnosing and critical position ( dead, alive or emigrated ) were found from the Office of National Statistics for each patient. However as there was no information available the socio-economic position of each malignant neoplastic disease patient, utilizing the ZIP code the abode at diagnosing of each malignant neoplastic disease patients was identified and hence a want mark based on the abode was allocated to each patient. Five want classs ( from 1 most affluent to 5 most deprived ) were categorise utilizing the income sphere mark of the 2004 Index of Multiple want ( IMD2004 ) and each patient was hence assigned to their several class based on their want mark. The IMD is based on everyday administrative informations of the 34,378 Lower Super-Output Areas ( LSOAs ) in England.Carstairs indication ( 22 ) was the index used antecedently. comparing the IMD mark to the Carstairs mark, the IMD is based on a smaller geographical country and is non based the nose count informati ons and therefore can be updated on a regular base without packing out a new nose count. The IMD is normally updated every 3-4 old ages.2.2 Statistical Methods2.2.1 Relative Survival and Excess MortalityNet endurance can be used to mensurate malignant neoplastic disease mortality immediately. It can besides be used to mensurate extra mortality of malignant neoplastic disease patients compared to the general population.Net endurance can be estimated utilizing cause specific or extra mortality. Net endurance utilizing the cause-specific fill out can be used by measuring the cause of each decease, and the deceases attri stilled to the malignant neoplastic disease are considered and all other causes of deceases are censor. The major disadvantage is that there is a strong dependance on the quality of decease records.Cause-specific endurance can be used to mensurate malignant neoplastic disease mortality straight and uses within informations of all deceases, nevertheless the cause of decease in this instance is malignant neoplastic disease and is used in the malignant neoplastic disease mortality. This method requires the cause of decease to be accurate and exactly specified, nevertheless the cause of decease is non presumption in most instances. Indirect deceases such as deceases due to route accidents or deceases due to side- do of medications/treatment on board deceases due to malignant neoplastic disease are hard to sort. Furthermore, different diagnosticians will specify cause of decease otherwise depending on the state of affairs at nip of decease hence cause of decease may non be right defined.There are 2 methods of judgment of the cause specific attack are Kaplan-Meier method and the Acturial method.Excess mortality is a method which accounts for malignant neoplastic disease mortality straight and indirectly without necessitating an accurate and precise specification of the cause of decease ( 23 ) . The extra mortality is derived as the differenc e in the ascertained mortality ( mortality due to all causes ) and expected mortality ( mortality due to non-cancer-related causes ) .Both extra mortality methods devotion malignant neoplastic disease mortality after seting for background mortality from assorted other causes and hence presumptively should give similar values. In world nevertheless this depends on how suitably premises are fulfilled for each several method, chiefly accurately documenting and stipulating the cause of decease for the cause-specific method and the truth of gauging the expected mortality for the extra mortality method ( 23 ) .Excess mortality is separate mathematically utilizing the jeopardy stage at trimming since diagnosing as. The jeopardy map is equal to the amount of the extra jeopardy due to stomach malignant neoplastic disease diagnosing and the expected jeopardy ( sometimes known as the baseline jeopardy, estimated utilizing external informations from the general population ) where is the c ovariates sender ( 24 ) . equivalence ( 1 )Net endurance ( Relative endurance ) is the survival corresponding to extra mortality, and is derived as the ratio of the ascertained endurance of the malignant neoplastic disease patients to the expected endurance estimated from the general population utilizing life tabular arraies. Equation ( 1 ) may therefore equivalently be written in footings of net/ coition endurance asEquation ( 2 )where and are the cumulative observed and expected endurance severally. The notification between the jeopardy map and expected jeopardy and cumulative observed and expected endurance severally, is given by and, and the net/relative endurance is so given as. ( 24 )The jeopardy is assumed to be piecewise constant over of revaluation coiffure ( changeless over little decorate intervals ) in pattern and hence a short period such as a class or less might be used at the start of the reappraisal. If a longer period is used so the changeless jeopardy premi se is violated and graze since diagnosing is non automatically adjusted for and is hence the unceasing map may be modelled as a measure map. A new covariate vector is derived by adding the covariate vector with the index variables where the index variables are generated for all intervals apart from the note interval. A multiplicative map of the covariates in the signifier of is assumed to be the extra jeopardy and therefore equation ( 1 ) becomesEquation ( 3 )or insteadEquation ( 4 )where the parametric quantity estimates when exponentiated can be inferred as extra jeopardy ratios ( EHRs ) . The jeopardies are assumed to be relative implicitly in equation ( 3 ) . By Introducing interaction footings of the follow-up clip and covariates in the conjectural account can be used for patterning non- symmetricalnessal jeopardies.Excess mortality can be estimated utilizing assorted different methods,Different methods exist for gauging extra mortality, either utilizing a full likelihood attack ( 25 ) , or based on sorted informations incorporating one observation for each life table interval within a generalised running(a) suppositious account ( 25, 26 ) .Life tabular arraies provide information on endurance and give the chance of decease in the general population stratified by age, calendar twelvemonth, sex, want and authorities office part ( GOR ) . The life tabular arraies in England are based on the nose count informations and are hence updated every 10 old ages to demo alterations in life anticipation.In the analysis carried out for this undertaking the life tabular array used is stratified by sex, age, GOR, twelvemonth of issue, and IMD quintile.The Life tabular arraies from 1981-2010 were used. Life tabular arraies are based on mortality in the general population, which include the mortality due to stomach malignant neoplastic disease, but because decease due to malignant neoplastic disease is little compared to the general population, it does non impact net/relative endurance estimations in pattern Ederee et Al. ( 27 ) .The stpm2 bid in STATA was used to foretell comparative endurance. The timescale and failure were declared utilizing the stset bid, and the clip beginning for the analysis was taken to be the day of the month of diagnosing of each topic. The timescale was calculated in old ages and the extra mortality was modelled as the particular result of involvement as suggested in ( 23 ) .2.2.2 SplinesFrequently complex non-linear effects from uninterrupted variables e.g. age are modelled in arrested development theoretic accounts. There are many another(prenominal) improved methods of patterning complex and non-linear effects. Splines is an easy manner of including an explanatory variable in a smooth non-linear manner.Mathematical maps which are sections of multinomials and coupled together at points called knots are known as splines. To do the spline smooth, A figure of restraints which include limitations on the mathemati cal derived functions of the spline map are applied between next multinomial sections so that the skid is smooth at the knot.In general, splines can be generated utilizing multinomials of any grade. However three-dimensional splines are frequently used, in which each section can be written as a three-dimensional multinomial as three-dimensional multinomials normally model most curves right and are computationally easy to obtain. The smoothness status for a three-dimensional spline promoter that the spline map is uninterrupted i.e. the first and 2nd derived functions are uninterrupted everyplace and there are no leaps or interruptions in the spline.A three-dimensional spline with K knots may be derived mathematically in footings of K+4 parametric quantities in general as ( 28 ) where the notation classifies the incline map, where if, and if and the knots are at places severally.Cubic splines behave ill at the dress suits when fitted to informations is less and the spline map may be susceptible to extreme value. A subset of three-dimensional splines where the spline map is additive before the first knot and after the last knot are known as restricted splines ( 28 ) . A restricted three-dimensional spline can be specified by K-1 parametric quantities for K figure of knots which is 5 less than a general three-dimensional spline.where the is defined asWith a logarithmically transformed clip variable, restricted splines are normally used to pattern the extra jeopardy. Knots can be anywhere on the log-outcome clip distribution, where the boundary knots at the first and last log-outcome clip.2.2.3 negotiable Parametric Survival ModelsRoyston and Parmar ( 29 ) foremost introduced flexible parametric theoretical accounts in the position of censored endurance informations. This method of patterning informations gave more tractability to the form of the jeopardy map in comparing to other parametric theoretical accounts e.g. the Weibull theoretical account for which t he signifiers of the jeopardy map are limited.The flexible parametric theoretical accounts do non necessitate numerical incorporation and hence a cardinal advantage of such theoretical accounts is comparatively quick calculations. ( 30 )The Cox theoretical account is the most common method of covering with censored informations, nevertheless flexible parametric theoretical accounts can cover with non- remainderal jeopardies more expeditiously.In flexible parametric endurance theoretical accounts, clip is treated as a uninterrupted variable and hence unlike piecewise approaches the demand of dividing the time-scale is non needed ( 24, 26 ) . The gigantic Numberss of excess parametric quantities which are required to be created so that time-dependent effects are integrate in the piecewise attack are hence non required in this example attack and hence this reduces the computational clip and uses less computing cable car memory particularly for big datasets.Alteration of the flex ible parametric theoretical accounts have since been done for comparative endurance theoretical accounts ( 30, 31 )A parametric theoretical account is defined as a theoretical account which can be identified in footings of a better set of parametric quantities ( , , ) . Restricted three-dimensional splines are fitted to the estimations of the log baseline jeopardy in a flexible parametric net/relative endurance theoretical account ( 30 ) .Equation ( 6 )Transforming to the endurance graduated tableEquation ( 7 )where is the restricted three-dimensional spline map of with knots, and is the cumulative overall jeopardy. The log-likelihood map is obtained utilizing equation ( 6 ) and numerical methods are used to gauge the parametric quantities which give upper limit likeliness utilizing equation. Thus the endurance and hazard maps can be analytically estimated.2.2.4 Evitable DeathsA manner of infering extra hazard ratios is by forecasting evitable deceases ( 32-34 ) . The figure of evitable deceases is the figure of deceases due to stomach malignant neoplastic disease which could be avoided if the net endurance in all socio-economic classs would be the alike(p)(p) as that of the most flush class after seting for the different features of each class.The expected figure of deceases due to all causes amongst a specific group of patients utilizing equation ( 2 ) iswhere N is the size of the population, is the expected endurance at clip T and is the net endurance of the concerned group at clip T.In the general population, the predicted figure of all-cause deceases in a matched group is.The premise of net endurance being the same as in a population being compared to is made ( in this instance the to the lowest degree disadvantaged ( flush ) category ) to deduce evitable deceases.The figure of evitable deceases are calculated by deducting the predicted figure of deceases due to all causes given the new comparative endurance from the predicted figure of deceases due to all causes given the original comparative endurance.The figure of evitable deceases represents postponed deceases which will happen afterwards and hence are rightfully variable with the follow-up clip.2.3 Statistical AnalysisTo transport out the statistical analysis, informations were examined to vouch it s dependability. Consistency cheques were besides carried to do certain informations was placed in the needed scopes. Datas from the Hospital Episode Statistics ( HES ) database were merged with the malignant neoplastic disease register informations, and information on intervention was obtained. patients whose records could non be matched to the HES database were excluded. Patients who had losing informations on variables such as GOR or IMD mark ( used to deduce want classs ) , which were used in unifying with the general population life tabular array to gauge the net endurance were besides excluded from the analysis.The patient distributions were examined by the chief expl anatory variables on the information.To happen differences in want class, cross-tabulations of other variables ( such as intervention, GOR and malignant neoplastic disease registers etc. ) by want category were carried out.Net endurance by want category was estimated utilizing a flexible parametric theoretical account. This theoretical account did non affect any variables with losing informations and the stpm2 bid in STATA was used to cipher predicted net endurance. Expected chances of decease were estimated by unifying the life tabular arraies stratified by age, sex, want and GOR and twelvemonth of issue, to the malignant neoplastic disease dataset ( formed of HES merged with the malignant neoplastic disease register informations ) .The method of flexible parametric theoretical accounts utilizing restricted three-dimensional splines was used, as this method was computationally less ambitious and less clip consuming and a more accurate method of analysis. Using flexible parametric p atterning with splines, interaction footings were fitted in the theoretical account. As extra mortality was predicted to differ non-linearly with age, hence interaction footings for age with splines were besides introduced.To prove the rightness of this method of analysis, both in footings of the procedure of utilizing splines and besides presenting the interaction footings of the theoretical account. Net endurance for up to 10 old ages was estimated and predicted by want category, seting for sex, intervention and age group. A new variable dividing the age with 5 splines was so created and used to do dummy variables for the restricted three-dimensional age splines variables. A restricted three-dimensional spline with 5 knots was used.To let for non-proportionality in the extra jeopardy for both twelvemonth ( twelvemonth of diagnosing ) spline and age spline variables, dummy variables for the interaction between both variables were generated.A figure of flexible parametric theoretica l accounts were fitted for males and females individually. The first theoretical account was fitted with want and chief confounders such as the age splines and twelvemonth ( twelvemonth of diagnosing ) splines. A 2nd theoretical account with interactions between age splines and twelvemonth ( twelvemonth of diagnosing ) splines every bit good as utilizing all the variables from the first theoretical account. The 3rd theoretical account was fitted by including intervention ( as the association between intervention and want class was to be examined particularly in patients who had surgery ) in the scoop up adjustment theoretical account out of the first two theoretical accounts. The theoretical accounts were re-fitted with clip changing effects with age merely and so with both age and clip of diagnosing. These theoretical accounts were compared for the best of tantrum utilizing the likeliness ratio trial.To happen out which grades of liberty ( DF ) for the baseline jeopardy produced the better adjustment theoretical account, the best adjustment theoretical account without the clip changing effects was fitted with 1 to 5 DF and so compared utilizing Akaike information standard ( AIC ) and Bayesian information standard ( BIC ) . The best allowance theoretical account with the DF for the baseline jeopardy was chosen to be the 1 with the smallest AIC and BIC. The same method was used to make up ones mind which DF for the varying effects was best used for the best fitting clip changing effects theoretical account.The scrutiny of evitable deceases was carried out to gauge and foretell the figure of evitable deceases at 1 and 5 old ages if endurance was the same in all want classs as the most flush class.3 Consequences3.1 Description of the malignant neoplastic disease register informationsFor the analyses to be carried out, a sum of 70,370 patients who were diagnosed with tummy malignant neoplastic disease during the period of 1997-2006, and were linked to the HES database. From the entire figure of patients, 1729 ( 2.46 % ) patients were registered via their decease certification merely ( DCO ) or had zero endurance ( day of the month of decease was the same as the day of the month of diagnosing ) . Zero endurances were included in the analysis by adding one twenty-four hours to the day of the month of decease, as excepting them would overrate the endurance, nevertheless it is known that DCOs seldom have a corroborate day of the month of diagnosing ( 21 ) .Of the entire figure of tummy malignant neoplastic disease patients, 45,580 ( 64.77 % ) were work forces and 24,790 ( 35.23 % ) of the patients were adult females. dodge shows the figure of tummy malignant neoplastic disease instances by GOR. The largest absolute figure of tummy malignant neoplastic disease patients was in the North- watt part and the smallest being in the North eastmost part. fudge Proportion of tummy malignant neoplastic disease patients by Government Office RegionGov ernment office partNumber ( % ) of patientsNorth East ( A )5,157 ( 7.33 )North West ( B )11,615 ( 16.51 )Yorkshire and The Humber ( D )8,710 ( 12.38 )East Midlands ( E )6,278 ( 8.92 )West Midlands ( F )8,461 ( 12.02 )East of England ( G )7,027 ( 9.99 )London ( H )7,508 ( 10.67 )South East ( J )8,878 ( 12.62 )South West ( K )6,736 ( 9.57 )The proportion of males to females and average age of tummy malignant neoplastic disease diagnosing were similar across all want categories, the highest stringent age at diagnosing in the in-between want class ( 73.3 old ages ) and the lowest amongst the most disadvantaged group and the flush group ( 72.4 old ages ) , nevertheless this difference in imply age at diagnosing was non that large amongst want categories. The spread for age amongst all want categories was found to be similar due to the lopsidedness and standard divergence. The proportions of topics coming from each GOR by want category differed mostly. double Percentage of patients by w ant categoryA clear monotonically increasing form was found in the per centum of people by want category, where there was a lower per centum of patients from the flush category and a higher per centum of patients from the disadvantaged category as shown in think 1.Figure Percentage of patients having no interventionA intention was correspondn in intervention. Figure 2 shows that the most disadvantaged group were less likely to have any signifier of intervention. The tendency in the per centum of patients having any intervention including surgery was found to back up the consequences from Figure 2, where the per centum of patients from flush to the most disadvantaged were 34.63 % , 34.30 % , 33.74 % , 33.02 % and 32.79 % severally. board Distribution of patients by Sexual activity anthropoidsFemalesEntire versatilesNitrogen%Nitrogen%Nitrogen%45,58064.7724,79035.2370370100 long time group ( old ages )15-441,0202.247062.851,7262.4545-542,7606.061,0724.323,8325.4555-647,27715.972,663 10.749,94014.1365-7414,99032.896,08724.5521,07729.9575-8414,99232.899,03136.4324,02334.1485-1004,5419.965,23121.109,77213.89Want1-least deprived7,03315.433,49714.1110,53014.9628,16917.924,22617.0512,39517.6139,24120.275,16020.8114,40120.46410,39922.815,72323.0916,12222.915-most deprived10,73823.566,18424.9516,92224.05TreatmentSurgery merely7,71816.934,34717.5412,06517.15Chemo merely6,26613.752,1148.538,38011.91Radio merely2330.511120.453450.49Surgery, wireless1350.30770.312120.30Surgery, chemo1,6883.707312.952,4193.44Chemo, wireless1140.25370.151510.21Surgery, chemo, wireless450.10130.05580.08No intervention29,38164.4617,35970.0246,74066.42SiteC16013,93230.574,52018.2318,45226.22C1616431.412901.179331.33C1621,1332.496002.421,7332.46C1632,2764.991,7467.044,0225.72C1641,0592.328123.281,8712.66C1653,2687.171,6886.814,9567.04C1661,2272.696862.771,9132.72C1684601.012501.017101.01C16921,58247.3514,19857.2735,78050.85Government Office Region ( GOR )A3,2237.071,9347.805,1577.33Bacillus7,367 16.164,24817.1411,61516.51Calciferol5,46611.993,24413.098,71012.38Tocopherol4,1829.182,0968.466,2788.92F5,66912.442,79211.268,46112.02 yard4,74610.412,2819.207,0279.99Hydrogen4,74510.412,76311.157,50810.67Joule5,80212.733,07612.418,87812.62K4,3809.612,3569.506,7369.57Cancer RegistryNorth & A York7,45516.364,43117.8711,88616.89Trent5,27711.582,79911.298,07611.48East Anglia3,1486.911,4745.954,6226.57Thames9,36820.555,20220.9814,57020.70Oxford1,8153.981,0024.042,8174.00South & A West5,87612.893,06312.368,93912.70West Midlands5,97512.432,79011.258,45612.02North West & A Mersey6,97515.304,0294.02911,00415.64From prorogue 2, it can be intelligibly seen that the proportion of males and females were similar in the two youngest age group classs, nevertheless the proportion of males was more in the in-between two classs and the proportion of females was more in the oldest two classs. The distribution of the proportion of males and females was similar for all want, intervention, GOR and m alignant neoplastic disease register classs. The proportion of males was about twice every bit many as females for site C160 and the proportion of females was more compared to males for site C169, nevertheless the proportion of males and females were similar for all other sites.A important factor in finding endurance is intervention, hence a trial was carried out to see if there was any difference between want classs in the proportion having any intervention compared to those non having intervention, and in the proportion having intervention affecting surgery compared to those undergoing no surgical intervention. Two logistic arrested development theoretical accounts were hence carried out, one for the proportion having any intervention and the other for the proportion having surgical intervention by want class, seting for age and twelvemonth of diagnosing, individually for males and females. aft(prenominal) seting for confounder, the odds of acquiring any intervention for females i n the most disadvantaged class were 0.88 times less than in the flush class ( p-value 0.009 ) . There was no difference in the odds of intervention in males between want classs.After seting for confounders, the odds having surgical intervention in males from the more disadvantaged classs was 1.18 times more than in the flush class ( p-value & lt 0.001 ) and no difference in the odds of having surgical intervention in females between want classs.The average age at diagnosing was 72.92 old ages. The mean overall follow-up clip of 1.57 old ages as shown in table 3. The per centum of patients who died by the storage of the follow-up period was found to be 91.64 % of patients.Table 3 shows the average follow-up clip ( the norm clip until stomach malignant neoplastic disease patients are dead or censored ) and the per centum of those who died stratified by age group, want category and intervention. A really little difference was found in both overall mean follow-up clip and the proporti on dead by the terminal of followup between males and females. The average follow-up clip was longer and the proportion of patients deceasing by the terminal of the followup was lower in younger topics. The average follow-up clip was longer and the proportion of patients deceasing was lower in the patients belonging to the most flush class, with both results demoing an diminishing tendency by diminishing want category.The average follow-up clip of patients having surgery, with either or both radiation therapy and chemotherapy, was longer than those patients who did non have surgery and the proportion death by the terminal of followup was smaller. This was chiefly due to the fact that chemotherapy and radiation therapy interventions were carried out on patients at the ulterior phases of the malignant neoplastic disease, whereas surgery was carried out before phase, nevertheless this may propose that patients who underwent surgery had a better endurance.VariableAverage followup ( old ages )% dead by the terminal of followupMaleFemaleOverallMaleFemaleOverall1.581.561.5791.7491.4591.64 mature group ( old ages )15-442.632.952.7680.3974.5077.9845-542.472.552.4983.6280.7882.8355-642.252.512.3285.8382.5884.9665-741.761.991.8390.4397.9389.7075-841.131.291.1995.9694.5995.4485-1000.620.640.6399.1099.1499.12Want1-least deprived1.761.801.7789.9589.3389.7421.651.581.6391.4690.9191.2731.561.521.5492.1491.9892.0841.481.501.4992.3691.9492.225-most deprived1.531.481.5192.1892.1292.16TreatmentSurgery merely3.413.703.5277.5274.7676.53Chemo merely1.581.481.5594.1494.8094.31Radio merely1.701.401.6090.5691.0790.72Surgery, wireless3.824.674.1376.3061.0470.75Surgery, chemo3.263.253.2681.4680.8581.27Chemo, wireless1.842.021.8992.1189.1991.39Surgery, chemo, wireless3.133.273.1686.6784.6286.21No intervention0.990.940.9795.6495.8295.71Table 3 Average follow-up clip and % of patients who were recorded as holding died by the terminal of the follow-up period by sex3.2 Consequences from the more complex analysisThe fair flexible parametric theoretical account was fitted with want, age splines and twelvemonth splines variables. The grades of freedom for the baseline jeopardy were chosen utilizing the AIC and BIC consequences from Table 4.Table 4 Degrees of freedom for service line jeopardy and their AIC/BICservice line Hazard DFModel DFAICBICMale11692327.5092467.1321787329.5987477.9531886419.8886576.9741986097.2186263.0352085890.8386065.38Female11644135.4544265.3421741201.0741339.0831840783.5440929.6741940686.4540840.6952040568.3140730.67From Table 4, it can clearly be seen that the theoretical accounts fitted with 5 grades of freedom for the baseline jeopardy give the smallest AIC and BIC for both males and females and hence provide a better tantrum for the theoretical account. Although it seems best to utilize 5 DF for the baseline jeopardy, 3 DF will be used as the theoretical accounts with 5 DF are computationally intensive when clip changing effects are included.T able 5 Net endurance by want class at 1, 5 and 10 old ages unadjusted for intervention for males and females individuallyNet enduranceMalesFemales1-year endurance almost flush0.360.3820.340.3530.330.3440.320.33 just about disadvantaged0.320.335-year enduranceMost flush0.160.1920.140.1630.130.1640.120.15Most disadvantaged0.120.1510-year enduranceMost flush0.120.1520.100.1230.100.1240.090.11Most disadvantaged0.090.11Consequences from the estimation of cyberspace endurance up to 1, 5, and 10 old ages after diagnosing, unadjusted for intervention, are shown in Figures 3-8 for males and females individually, and showed that there was a suggestion of a additive tendency across the want groups. Between the five want groups, 1-year predicted net endurance ranged from 0.32 to 0.36 for males and 0.33 to 0.38 for females. The 5-year predicted net endurance ranged from 0.12 to 0.16 for males and 0.15 to 0.19 in females. The 10- twelvemonth predicted net endurance ranged from 0.09 and 0.12 for m ales and 0.11 to 0.15 for females ( Table 5 ) . In general, the predicted cyberspace endurance scope had a somewhat higher lower limit and upper limit for females than males bespeaking that the predicted cyberspace endurance was overall better/higher in females than males.The estimated difference in endurance was 0.04 in males and 0.05 in females between the most flush and the most disadvantaged groups at one twelvemonth after diagnosing. At five old ages after diagnosing the estimated difference in endurance between the two groups was the same for males but decreased to 0.04 for females. A clear additive tendency was seen between one and five old ages after diagnosing. The tendency between the least disadvantaged and most disadvantaged classs remained up to ten old ages after diagnosing, although at ten old ages the endurance of the two most disadvantaged classs was the same.Table 6 Excess jeopardy ratio ( EHR ) of decease, adjusted for age and twelvemonth of diagnosing for males a nd females individually without seting for intervention and clip varying effects for patients diagnosed with tummy malignant neoplastic disease during 1997-2006 in EnglandMalesFemalesEHRP-value95 % CIEHRP-value95 % CIWant1-Least deprived baselineBaseline21.0460.014( 1.009, 1.084 )1.0720.006( 1.020, 1.128 )31.076& lt 0.001( 1.039, 1.114 )1.0820.001( 1.031, 1.136 )41.117& lt 0.001( 1.079, 1.155 )1.118& lt 0.001( 1.066, 1.172 )5-most deprived1.142& lt 0.001( 1.103, 1.181 )1.143& lt 0.001( 1.091, 1.197 )Splines13.389& lt 0.001( 3.349, 3.428 )3.383& lt 0.001( 3.331, 3.436 )21.242& lt 0.001( 1.230, 1.254 )1.262& lt 0.001( 1.246, 1.278 )31.107& lt 0.001( 1.101, 1.113 )1.098& lt 0.001( 1.090, 1.106 )Table 6 shows a comparing of the consequences of the flexible theoretical accounts for males and females individually. Comparing the consequences of males and females, the extra jeopardy ratio ( EHR ) of decease by want class was higher in general for females, although both analyses g ave a additive tendency in EHR by want. For both males and females, the EHR of decease by want was statistically important indicating that the EHR differed for each want class compared to the most flush class. accordingly more disadvantaged groups had a higher extra mortality due to malignant neoplastic disease compared to the less disadvantaged groups. come along and twelvemonth of diagnosing were modelled as a non-linear effects, and were important in for the first three age splines for both males and females and were important for twelvemonth spline 1 and 4 in males and twelvemonth splines 1 & A 2 in females.Figure net endurance up to 1 twelvemonth after diagnosing, by want class at diagnosing for males diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Figure network endurance up to 1 twelvemonth after diagnosing, by want class at diagnosing for females diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Figure Internet en durance up to 5 old ages after diagnosing, by want class at diagnosing for males diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Figure Internet endurance up to 5 old ages after diagnosing, by want class at diagnosing for females diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Figure Internet endurance up to 10 old ages after diagnosing, by want class at diagnosing for males diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Figure Relative endurance up to 10 old ages after diagnosing, by want class at diagnosing for females diagnosed with tummy malignant neoplastic disease during 1997-2006 in England.Table 7 Degrees of freedom for Time Varying Component ( TVC ) and their AIC/BIC with baseline jeopardy of 3 DF.TVC DFModel DFAICBICMale12386047.8986248.6222886035.8586280.2243885727.0886058.7254385660.8786036.14Female12340628.0640814.7722840590.5940817.943840504.9640813.4554340515.3540864.43The flexi ble parametric theoretical account was fitted with want, age splines and twelvemonth splines variables and age splines as the clip changing consequence. The grades of freedom for the baseline jeopardy were chosen utilizing the AIC and BIC consequences from Table 4.From Table 7, it can clearly be seen that the theoretical account fitted for males with 5 DF for the clip variable consequence gives the smallest AIC and BIC, nevertheless the theoretical account fitted for females with 4 DF has the smallest AIC and BIC. Therefore either 4 DF or 5 DF can be used run the analysis for the clip changing effects and intervention. Further analysis was carried out utilizing 4 DF.Table 8 Adjusted extra jeopardy ratio ( EHR ) of decease for males and females individually seting for intervention and clip changing effects of age and twelvemonth of diagnosing for patients diagnosed with tummy malignant neoplastic disease during 1997-2006 in EnglandMalesFemalesEHRP-value95 % CIEHRP-value95 % CIWant1-L east deprivedBaselineBaseline21.080& lt 0.001( 1.042, 1.120 )1.0560.036( 1.004, 1.110 )31.111& lt 0.001( 1.073, 1.150 )1.095& lt 0.001( 1.043, 1.149 )41.167& lt 0.001( 1.128, 1.208 )1.124& lt 0.001( 1.072,1.179 )5-most deprived1.195& lt 0.001( 1.155, 1.236 )1.162& lt 0.001( 1.109, 1.217 )Splines13.639& lt 0.001( 3.593, 3.686 )3.783& lt 0.001( 3.709, 3.859 )21.219& lt 0.001( 1.206, 1.232 )1.243& lt 0.001( 1.223, 1.264 )31.100& lt 0.001( 1.093, 1.108 )1.112& lt 0.001( 1.102, 1.122 )TreatmentNo SurgeryBaselineBaselineSurgery0.327& lt 0.001( 0.317, 0.337 )0.311& lt 0.001( 0.298, 0.325 )No ChemoBaselineBaselineChemo0.732& lt 0.001( 0.711, 0.754 )0.826& lt 0.001( 0.788, 0.865 )No RadioBaselineBaselineRadio0.755& lt 0.001( 0.679, 0.839 )0.7640.001( 0.653, 0.894 )Age splinesAge spline11.304& lt 0.001( 1.285, 1.323 )1.295& lt 0.001( 1.269, 1.322 )Age spline 20.945& lt 0.001( 0.931, 0.959 )0.938& lt 0.001( 0.922, 0.956 )Age spline 31.0140.063( 0.999, 1.028 )1.0190.048( 1 .000, 1.039 )Age spline 40.9930.286( 0.980, 1.006 )0.9800.028( 0.963, 0.998 )Age spline 50.9870.044( 0.975, 1.000 )0.9990.896( 0.985, 1.014 )Year of diagnosing splinesYear spline10.923& lt 0.001( 0.912, 0.935 )0.929& lt 0.001( 0.914, 0.944 )Year spline 21.0160.012( 1.003, 1.028 )1.0050.567( 0.989, 1.021 )Year spline 30.9880.041( 0.976, 0.999 )0.9960.622( 0.980, 1.012 )Year spline 41.025& lt 0.001( 1.013, 1.038 )1.0120.140( 0.996, 1.029 )Year spline 51.0030.630( 0.991, 1.015 )1.0050.592( 0.988, 1.021 )Table 8 shows a comparing of the consequences of the clip changing effects theoretical account seting for want, age at diagnosing, twelvemonth of diagnosing and intervention for males and females individually. Comparing the consequences from the male analysis with the female, the extra jeopardy ratio ( EHR ) for decease by want was lower in females in general, although both analyses gave a additive tendency in EHR by want. Comparing the EHR for both analyses to consequences from Tabl e 6, it is clear that the EHR is lower when intervention and clip changing effects such as age and twelvemonth of diagnosing are taken into history.There was besides lessening in EHR for any intervention compared to no intervention nevertheless there was a big lessening in EHR of surgery compared to no surgery for both males and females. In both analyses, intervention with surgery was associated with increased net endurance compared to non-surgical intervention or no intervention. Age and twelvemonth of diagnosing were modelled as a time-dependent non-linear consequence, and were important for peculiar splines in both theoretical accounts.The additive tendency in want category remained and became more important, since the EHR in want classs for both males and females differed in comparing to the most flush group at the 5 % significance degree, as in the instance of the simpler analyses. Therefore more disadvantaged groups had a higher extra mortality due to malignant neoplastic dis ease compared to the less disadvantaged groups. The deficiency of an interaction term between want classs and splines in the concluding theoretical account suggests that the difference in comparative endurance between want groups did non alteration over the clip period of the survey.Figure Internet endurance up to 1 twelvemonth after diagnosing, by want class at diagnosing for males seting for intervention and clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 1 twelvemonth after diagnosing, by want class at diagnosing for females seting for intervention and clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 5 old ages after diagnosing, by want class at diagnosing for males seting for intervention and clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 5 old ages after diagnosing, by want class at diagnosing for females seting for intervention and cli p changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 10 old ages after diagnosing, by want class at diagnosing for males seting for intervention and clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 10 old ages after diagnosing, by want class at diagnosing for females seting for intervention and clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 10 old ages after diagnosing, by want class at diagnosing for males who had intervention affecting surgery, seting for clip changing effects and diagnosed during 1997-2006 in England.Figure Internet endurance up to 10 old ages after diagnosing, by want class at diagnosing for males who had intervention affecting surgery, seting for clip changing effects and diagnosed during 1997-2006 in England.Table 9 Net endurance by want class at 1, 5 and 10 old ages adjusted for intervention and surgery for males and females individually.MalesFemalesNet enduranceNet endurance from tummy surgeryNet enduranceNet endurance from tummy surgery1-year enduranceMost flush0.370.650.360.6720.340.630.340.6530.330.620.330.6440.320.610.320.63Most disadvantaged0.310.600.320.635-year enduranceMost flush0.160.420.170.4620.140.390.160.4430.140.380.150.4240.130.370.140.42Most disadvantaged0.130.360.140.4110-year enduranceMost flush0.120.360.130.4020.110.320.120.3730.100.320.110.3640.100.300.110.35Most disadvantaged0.100.300.110.35Consequences from the estimation of cyberspace endurance up to 1, 5 and 10 old ages after diagnosing, adjusted for intervention and clip changing affects, are shown in Figures 9-14 for males and females individually, and showed that there was a sug
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