human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Rheumatoid arthritis ( RA ) frequently causes  foot pain and swelling that affect ambulation . Pharmaceutical management of pain and disability is st and ard in clinical practice . The use of functional posted foot orthoses , as an adjunct to pharmaceutical treatment , is a promising treatment for managing  foot pain and disability in RA . Its effectiveness , however , has not been rigorously evaluated . We performed a double-blind clinical trial using foot orthoses vs. placebo orthoses in the management of the rheumatoid arthritic foot , while subjects continued customary treatment . On the basis of findings of no effect on disability and pain measures , this study indicates no benefit of functional posted foot orthoses over placebos Background Conservative management of foot problems in patients with rheumatoid arthritis ( RA ) may consist of the prescription of customised foot orthoses . Indications for foot orthoses are not clear and the effectiveness of the intervention is highly variable among patients . Knowledge on which patients benefit the most from foot orthoses can help to select patients eligible for this type of intervention . The objective of the present study was to determine clinical and demographic factors that predict the outcome of customised foot orthoses on pain and disability in patients with RA . Methods A total of 135 RA patients who were supplied with customised foot orthoses were included in this prospect i ve cohort study . Pain and disability were measured before and after the intervention period using a Numeric Rating Scale ( NRS ) for foot pain , the Foot Function Index ( FFI ) , the Western Ontario and McMasters Universities Osteoarthritis Index ( WOMAC ) and a 10-meter walking test . The intervention period consisted of one or more appointments with the podiatrist during which the foot orthoses were customised . Swollen foot joint count , foot deformity scores , forefoot peak pressure , disease duration , age , gender , body mass index and baseline values of the outcome measures were selected as potential factors predicting outcome . Multivariate linear regression analyses were performed to determine factors associated with change in pain and disability ( at P < 0.05 ) . Results Disease duration was negatively associated with the change scores in NRS foot pain ( P = 0.018 ) , WOMAC pain ( P = 0.001 ) , FFI disability ( P = 0.003 ) and WOMAC physical function ( P = 0.002 ) . Age was negatively associated with the change score in 10 meter walking time ( P = 0.008 ) . For all outcome measures baseline values were positively associated with the change scores ( P < 0.001 ) . Conclusions Shorter disease duration predicted greater improvements in self-reported foot pain and disability , and younger age predicted greater improvements in walking time after intervention with foot orthoses . Also , higher baseline values of pain and disability predicted greater improvements . Referral for conservative management with foot orthoses in the early stage of RA seems important when aim ing to achieve reduction in pain and improvement in daily activities Purpose . To compare the effectiveness of functional foot orthoses and unshaped ( flat ) orthotic material on plantar pressure redistribution , forefoot pain reduction and walking ability in rheumatoid arthritis ( RA ) patients . Methods . Forty patients with RA were r and omised  to receive unshaped material ( UM ) ( n = 20 ) or functional foot orthoses ( n = 20 ) . Plantar pressure measurement was performed with an F-scan system . Foot pain was assessed by the pain subscale of the Foot Function Index . Walking ability was assessed by the 6-min walking test . Investigations were performed at baseline , 1 week after the patient received shoes with orthoses and 6 months later . Results . Plantar pressures were significantly higher at painful than at non-painful foot areas . No differences in plantar pressure redistribution were found between the groups . Notable reduction of pain and improvement of activity ( walking ability ) was observed in both groups . Foot pain has moderate impact on the walking ability of RA patients . Conclusions . The study showed no clear advantage of functional foot orthoses over UM Background Controlled clinical trials of health care interventions are either explanatory or pragmatic . Explanatory trials test whether an intervention is efficacious ; that is , whether it can have a beneficial effect in an ideal situation . Pragmatic trials measure effectiveness ; they measure the degree of beneficial effect in real clinical practice . In pragmatic trials , a balance between external validity ( generalizability of the results ) and internal validity ( reliability or accuracy of the results ) needs to be achieved . The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention . The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized . However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability . We are conducting two pragmatic r and omized controlled trials on interventions in the management of hypertension in primary care . We describe the design of the trials and the steps taken to deal with the competing dem and s of external and internal validity . Discussion External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions . Internal validity is maximized by decreasing contamination bias through cluster r and omization , and decreasing observer and assessment bias , in these non-blinded trials , through baseline data collection prior to r and omization , automating the outcomes assessment with 24 hour ambulatory blood pressure monitors , and blinding the data analysis . Summary Clinical trials conducted in community practice s present investigators with difficult method ological choices related to maintaining a balance between internal validity ( reliability of the results ) and external validity ( generalizability ) . The attempt to achieve method ological purity can result in clinical ly meaningless results , while attempting to achieve full generalizability can result in invalid and unreliable results . Achieving a creative tension between the two is crucial BACKGROUND Insoles are regarded as an appropriate tool for the management of rheumatic foot disorders . However , a quality control for this purpose has not been established . In our study , the clinical effectiveness of insoles used in patients with rheumatic foot disorders was addressed . In addition , we sought to establish pedobarography as a means of quality control for orthotic management of the rheumatic foot . MATERIAL AND METHODS Our study included 20 rheumatoid arthritis patients with painful rheumatic foot deformities who were provided with insoles .  Clinical data were obtained by physical examination and a 100-mm pain scale . Pedobarography was performed using the novel pedar cable system with new and individually design ed insoles and after a 6-month follow-up . A shoe-only trial served as control . The parameters maximum force , peak pressure , force-time integral , and average pressure were analyzed in anatomical regions and an individually defined overloaded forefoot region . RESULTS Clinical improvement was significant after a 6-month follow-up in spite of a heterogeneous group of patients . However , our results could not confirm consistent changes in plantar pressure distribution . CONCLUSION As a conclusion , further efforts are necessary to establish a quality control for orthotic management of the rheumatic foot OBJECTIVE To investigate the clinical effectiveness of early foot orthosis intervention for painful correctable valgus deformity of the rearfoot in rheumatoid arthritis ( RA ) . METHODS Patients with RA were r and omized to receive custom manufactured rigid foot orthoses under podiatry supervision ( n = 50 ) or enter a control group ( n = 48 ) . The control group received foot orthoses only when prescribed under normal medical care . Foot pain and disability , using the Foot Function Index ( FFI ) , along with disease activity , tolerance , and adverse reactions , were serially measured over 30 mo continuous treatment . RESULTS The group assigned foot orthoses demonstrated an immediate clinical improvement , the effect peaking at 12 mo . At 30 mo the FFI total score was reduced by 23.1 % from baseline in the intervention group . Area under the curve analysis showed a statistically significant reduction in FFI scores for total score ( p = 0.026 ) , foot pain ( p = 0.014 ) , and foot disability ( p = 0.016 ) when intervention was compared to control scores . There were no confounding effects from differences between groups for disease activity or pharmacological or other management strategies . Most patients ( 96 % ) used their orthoses and most found them comfortable ( 97 % ) , although minor adverse reactions , such as tender spots , blisters , and callus , were reported in 30 % of patients in the early stages of treatment and persisted in 12 % for 30 mo . CONCLUSION Custom design ed foot orthoses used continuously over a 30 mo treatment period result ed in a reduction in foot pain by 19.1 % , foot disability by 30.8 % , and functional limitation by 13.5 % . Clinical effectiveness might be enhanced by their use in the early stages of rearfoot pain and deformity OBJECTIVE To determine the effects of specialized shoes with insoles in patients with rheumatoid arthritis and the differences in terms of type of insole and anatomical location of foot pathology . DESIGN Single-blinded r and omized controlled trial . SETTING Out patients of physical medicine and rehabilitation clinic at university hospital . SUBJECTS Forty-two patients with rheumatoid foot lesions were r and omly assigned to two different orthotic intervention groups . The anatomical locations of the foot lesions were recorded ( hindfoot or forefoot ) . INTERVENTION Participants were provided with an extra deep forefoot-rockered shoe and either a custom-made semi-rigid insole or a ready-made simple soft insole . They wore the provided footwear for at least 3 hours a day over six months . MAIN OUTCOME MEASURES Primary outcome measures were foot pain visual analogue scale ( VAS ) scores and Foot Function Index ( FFI ) . Secondary outcome measures were erythrocyte sedimentation rate and C-reactive protein levels in blood , amounts of medications and active joint counts . These were checked at baseline and post intervention . RESULTS Eight patients dropped out at follow-up after six months of treatment . At six-month follow-ups , VAS scores and total Foot Function Index scores had decreased significantly in both groups versus baseline but intergroup comparison showed no significant differences in view of type of insoles and anatomical locations of foot pathology . CONCLUSIONS We were unable to identify differences between the types of insoles in terms of their clinical effects or between anatomical locations of foot lesions in the two groups , but both groups improved . Therapeutic shoes plus soft insoles might be effective enough in terms of foot pain and foot function for specific patients with rheumatoid foot problems regardless of the location of foot pathology OBJECTIVE To evaluate the efficacy of custom foot orthoses for the management of  painful rearfoot valgus in patients with rheumatoid arthritis ( RA ) . METHODS Patients were r and omized to receive custom-manufactured rigid carbon graphite foot orthoses ( RA-orthosis ) or enter a control group ( RA-control ) receiving no orthotic intervention .  Three-dimensional ( 3D ) kinematics were measured at the ankle joint complex ( AJC ) using an electromagnetic tracking ( EMT ) system under barefoot , shod , and orthosis walking conditions . Previously established normal 3D kinematic data were used to descriptively compare motion patterns in both RA groups and statistical analyses were performed on integrals of motion-time for each axis of rotation from data collected at baseline , 3 , 6 , 12 , 18 , 24 , and 30 months . RESULTS Compared with healthy control subjects , all patients with RA demonstrated excessive subtalar joint eversion motion through the stance phase of gait ( p < 0.0001 ) coupled with excessive internal leg rotation ( p < 0.0001 ) . Custom-manufactured orthoses significantly reduced eversion through stance ( p = 0.009 ) and re-established equilibrium of motion relative to neutral joint position . Correcting the frontal plane component of the deformity did not lead to a significant reduction in internal leg rotation ( p = 0.294 ) . The devices had no effect on tibiotalar dorsiflexion/plantarflexion ( p = 0.960 ) . Prospect ively , the rigid orthoses maintained and then improved the reduction in cumulative subtalar eversion motion ( p < 0.0001 ) . Minimal changes in cumulative subtalar component eversion and internal leg rotation were recorded for both RA groups when walking barefoot but the effect was significantly less for the RA-control group . From 12 months onwards , internal leg rotation started to decrease , suggesting re-coupling of motion , but the overall motion pattern remained abnormal in comparison with normal reference values . CONCLUSION These results support the continuous use of custom-manufactured foot orthoses to correct deformity and optimize AJC function in RA patients with early painful deformity of the rearfoot Hallux valgus deformity is the most commonly observed forefoot deformity in patients with rheumatoid arthritis . This 5-year , double-blind , r and omized clinical trial compared treatment orthoses with placebo orthoses for the prevention of hallux valgus deformity in the rheumatoid arthritic foot . One hundred and two subjects with active rheumatoid arthritis and with foot pain and minimal radiographic changes of the feet participated in the study . They were recruited from five arthritis clinics in the Chicago metropolitan area that are affiliated with or are teaching clinics of area medical schools . Patients were followed for 3 years . Eighty-one subjects completed the study . In a logistic regression analysis , the treatment group was 73 % less likely to develop hallux valgus deformity compared with the control group ( adjusted odds ratio 0.27 , 95 % confidence interval 0.078 , 0.916 p = .04 ) . These findings suggest that foot orthoses can prevent or slow the progression of hallux valgus deformity OBJECTIVES Prescribing foot orthotics in rheumatoid arthritis patients with symptomatic forefoot involvement is a st and ard practice . However , limited research has been reported regarding gait and pain improvement with the use of foot orthotics . PATIENTS AND METHO 
    Output:
    
agent
There was weak evidence for  custom orthoses reducing pain and forefoot plantar pressures .
Evidence was inconclusive for foot function , walking speed , gait parameters , and reducing hallux abductovalgus angle progression .
CONCLUSION Custom orthoses may be beneficial in reducing pain and elevated forefoot plantar pressures in the rheumatoid foot and ankle .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Rheumatoid arthritis ( RA ) frequently causes  foot pain and swelling that affect ambulation . Pharmaceutical management of pain and disability is st and ard in clinical practice . The use of functional posted foot orthoses , as an adjunct to pharmaceutical treatment , is a promising treatment for managing  foot pain and disability in RA . Its effectiveness , however , has not been rigorously evaluated . We performed a double-blind clinical trial using foot orthoses vs. placebo orthoses in the management of the rheumatoid arthritic foot , while subjects continued customary treatment . On the basis of findings of no effect on disability and pain measures , this study indicates no benefit of functional posted foot orthoses over placebos Background Conservative management of foot problems in patients with rheumatoid arthritis ( RA ) may consist of the prescription of customised foot orthoses . Indications for foot orthoses are not clear and the effectiveness of the intervention is highly variable among patients . Knowledge on which patients benefit the most from foot orthoses can help to select patients eligible for this type of intervention . The objective of the present study was to determine clinical and demographic factors that predict the outcome of customised foot orthoses on pain and disability in patients with RA . Methods A total of 135 RA patients who were supplied with customised foot orthoses were included in this prospect i ve cohort study . Pain and disability were measured before and after the intervention period using a Numeric Rating Scale ( NRS ) for foot pain , the Foot Function Index ( FFI ) , the Western Ontario and McMasters Universities Osteoarthritis Index ( WOMAC ) and a 10-meter walking test . The intervention period consisted of one or more appointments with the podiatrist during which the foot orthoses were customised . Swollen foot joint count , foot deformity scores , forefoot peak pressure , disease duration , age , gender , body mass index and baseline values of the outcome measures were selected as potential factors predicting outcome . Multivariate linear regression analyses were performed to determine factors associated with change in pain and disability ( at P < 0.05 ) . Results Disease duration was negatively associated with the change scores in NRS foot pain ( P = 0.018 ) , WOMAC pain ( P = 0.001 ) , FFI disability ( P = 0.003 ) and WOMAC physical function ( P = 0.002 ) . Age was negatively associated with the change score in 10 meter walking time ( P = 0.008 ) . For all outcome measures baseline values were positively associated with the change scores ( P < 0.001 ) . Conclusions Shorter disease duration predicted greater improvements in self-reported foot pain and disability , and younger age predicted greater improvements in walking time after intervention with foot orthoses . Also , higher baseline values of pain and disability predicted greater improvements . Referral for conservative management with foot orthoses in the early stage of RA seems important when aim ing to achieve reduction in pain and improvement in daily activities Purpose . To compare the effectiveness of functional foot orthoses and unshaped ( flat ) orthotic material on plantar pressure redistribution , forefoot pain reduction and walking ability in rheumatoid arthritis ( RA ) patients . Methods . Forty patients with RA were r and omised  to receive unshaped material ( UM ) ( n = 20 ) or functional foot orthoses ( n = 20 ) . Plantar pressure measurement was performed with an F-scan system . Foot pain was assessed by the pain subscale of the Foot Function Index . Walking ability was assessed by the 6-min walking test . Investigations were performed at baseline , 1 week after the patient received shoes with orthoses and 6 months later . Results . Plantar pressures were significantly higher at painful than at non-painful foot areas . No differences in plantar pressure redistribution were found between the groups . Notable reduction of pain and improvement of activity ( walking ability ) was observed in both groups . Foot pain has moderate impact on the walking ability of RA patients . Conclusions . The study showed no clear advantage of functional foot orthoses over UM Background Controlled clinical trials of health care interventions are either explanatory or pragmatic . Explanatory trials test whether an intervention is efficacious ; that is , whether it can have a beneficial effect in an ideal situation . Pragmatic trials measure effectiveness ; they measure the degree of beneficial effect in real clinical practice . In pragmatic trials , a balance between external validity ( generalizability of the results ) and internal validity ( reliability or accuracy of the results ) needs to be achieved . The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention . The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized . However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability . We are conducting two pragmatic r and omized controlled trials on interventions in the management of hypertension in primary care . We describe the design of the trials and the steps taken to deal with the competing dem and s of external and internal validity . Discussion External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions . Internal validity is maximized by decreasing contamination bias through cluster r and omization , and decreasing observer and assessment bias , in these non-blinded trials , through baseline data collection prior to r and omization , automating the outcomes assessment with 24 hour ambulatory blood pressure monitors , and blinding the data analysis . Summary Clinical trials conducted in community practice s present investigators with difficult method ological choices related to maintaining a balance between internal validity ( reliability of the results ) and external validity ( generalizability ) . The attempt to achieve method ological purity can result in clinical ly meaningless results , while attempting to achieve full generalizability can result in invalid and unreliable results . Achieving a creative tension between the two is crucial BACKGROUND Insoles are regarded as an appropriate tool for the management of rheumatic foot disorders . However , a quality control for this purpose has not been established . In our study , the clinical effectiveness of insoles used in patients with rheumatic foot disorders was addressed . In addition , we sought to establish pedobarography as a means of quality control for orthotic management of the rheumatic foot . MATERIAL AND METHODS Our study included 20 rheumatoid arthritis patients with painful rheumatic foot deformities who were provided with insoles .  Clinical data were obtained by physical examination and a 100-mm pain scale . Pedobarography was performed using the novel pedar cable system with new and individually design ed insoles and after a 6-month follow-up . A shoe-only trial served as control . The parameters maximum force , peak pressure , force-time integral , and average pressure were analyzed in anatomical regions and an individually defined overloaded forefoot region . RESULTS Clinical improvement was significant after a 6-month follow-up in spite of a heterogeneous group of patients . However , our results could not confirm consistent changes in plantar pressure distribution . CONCLUSION As a conclusion , further efforts are necessary to establish a quality control for orthotic management of the rheumatic foot OBJECTIVE To investigate the clinical effectiveness of early foot orthosis intervention for painful correctable valgus deformity of the rearfoot in rheumatoid arthritis ( RA ) . METHODS Patients with RA were r and omized to receive custom manufactured rigid foot orthoses under podiatry supervision ( n = 50 ) or enter a control group ( n = 48 ) . The control group received foot orthoses only when prescribed under normal medical care . Foot pain and disability , using the Foot Function Index ( FFI ) , along with disease activity , tolerance , and adverse reactions , were serially measured over 30 mo continuous treatment . RESULTS The group assigned foot orthoses demonstrated an immediate clinical improvement , the effect peaking at 12 mo . At 30 mo the FFI total score was reduced by 23.1 % from baseline in the intervention group . Area under the curve analysis showed a statistically significant reduction in FFI scores for total score ( p = 0.026 ) , foot pain ( p = 0.014 ) , and foot disability ( p = 0.016 ) when intervention was compared to control scores . There were no confounding effects from differences between groups for disease activity or pharmacological or other management strategies . Most patients ( 96 % ) used their orthoses and most found them comfortable ( 97 % ) , although minor adverse reactions , such as tender spots , blisters , and callus , were reported in 30 % of patients in the early stages of treatment and persisted in 12 % for 30 mo . CONCLUSION Custom design ed foot orthoses used continuously over a 30 mo treatment period result ed in a reduction in foot pain by 19.1 % , foot disability by 30.8 % , and functional limitation by 13.5 % . Clinical effectiveness might be enhanced by their use in the early stages of rearfoot pain and deformity OBJECTIVE To determine the effects of specialized shoes with insoles in patients with rheumatoid arthritis and the differences in terms of type of insole and anatomical location of foot pathology . DESIGN Single-blinded r and omized controlled trial . SETTING Out patients of physical medicine and rehabilitation clinic at university hospital . SUBJECTS Forty-two patients with rheumatoid foot lesions were r and omly assigned to two different orthotic intervention groups . The anatomical locations of the foot lesions were recorded ( hindfoot or forefoot ) . INTERVENTION Participants were provided with an extra deep forefoot-rockered shoe and either a custom-made semi-rigid insole or a ready-made simple soft insole . They wore the provided footwear for at least 3 hours a day over six months . MAIN OUTCOME MEASURES Primary outcome measures were foot pain visual analogue scale ( VAS ) scores and Foot Function Index ( FFI ) . Secondary outcome measures were erythrocyte sedimentation rate and C-reactive protein levels in blood , amounts of medications and active joint counts . These were checked at baseline and post intervention . RESULTS Eight patients dropped out at follow-up after six months of treatment . At six-month follow-ups , VAS scores and total Foot Function Index scores had decreased significantly in both groups versus baseline but intergroup comparison showed no significant differences in view of type of insoles and anatomical locations of foot pathology . CONCLUSIONS We were unable to identify differences between the types of insoles in terms of their clinical effects or between anatomical locations of foot lesions in the two groups , but both groups improved . Therapeutic shoes plus soft insoles might be effective enough in terms of foot pain and foot function for specific patients with rheumatoid foot problems regardless of the location of foot pathology OBJECTIVE To evaluate the efficacy of custom foot orthoses for the management of  painful rearfoot valgus in patients with rheumatoid arthritis ( RA ) . METHODS Patients were r and omized to receive custom-manufactured rigid carbon graphite foot orthoses ( RA-orthosis ) or enter a control group ( RA-control ) receiving no orthotic intervention .  Three-dimensional ( 3D ) kinematics were measured at the ankle joint complex ( AJC ) using an electromagnetic tracking ( EMT ) system under barefoot , shod , and orthosis walking conditions . Previously established normal 3D kinematic data were used to descriptively compare motion patterns in both RA groups and statistical analyses were performed on integrals of motion-time for each axis of rotation from data collected at baseline , 3 , 6 , 12 , 18 , 24 , and 30 months . RESULTS Compared with healthy control subjects , all patients with RA demonstrated excessive subtalar joint eversion motion through the stance phase of gait ( p < 0.0001 ) coupled with excessive internal leg rotation ( p < 0.0001 ) . Custom-manufactured orthoses significantly reduced eversion through stance ( p = 0.009 ) and re-established equilibrium of motion relative to neutral joint position . Correcting the frontal plane component of the deformity did not lead to a significant reduction in internal leg rotation ( p = 0.294 ) . The devices had no effect on tibiotalar dorsiflexion/plantarflexion ( p = 0.960 ) . Prospect ively , the rigid orthoses maintained and then improved the reduction in cumulative subtalar eversion motion ( p < 0.0001 ) . Minimal changes in cumulative subtalar component eversion and internal leg rotation were recorded for both RA groups when walking barefoot but the effect was significantly less for the RA-control group . From 12 months onwards , internal leg rotation started to decrease , suggesting re-coupling of motion , but the overall motion pattern remained abnormal in comparison with normal reference values . CONCLUSION These results support the continuous use of custom-manufactured foot orthoses to correct deformity and optimize AJC function in RA patients with early painful deformity of the rearfoot Hallux valgus deformity is the most commonly observed forefoot deformity in patients with rheumatoid arthritis . This 5-year , double-blind , r and omized clinical trial compared treatment orthoses with placebo orthoses for the prevention of hallux valgus deformity in the rheumatoid arthritic foot . One hundred and two subjects with active rheumatoid arthritis and with foot pain and minimal radiographic changes of the feet participated in the study . They were recruited from five arthritis clinics in the Chicago metropolitan area that are affiliated with or are teaching clinics of area medical schools . Patients were followed for 3 years . Eighty-one subjects completed the study . In a logistic regression analysis , the treatment group was 73 % less likely to develop hallux valgus deformity compared with the control group ( adjusted odds ratio 0.27 , 95 % confidence interval 0.078 , 0.916 p = .04 ) . These findings suggest that foot orthoses can prevent or slow the progression of hallux valgus deformity OBJECTIVES Prescribing foot orthotics in rheumatoid arthritis patients with symptomatic forefoot involvement is a st and ard practice . However , limited research has been reported regarding gait and pain improvement with the use of foot orthotics . PATIENTS AND METHO 
    Output:
    