AIM:To assess the efficacy of ketotifen in treating allergic conjunctivitis.METHODS:A systematic search of systematic reviews and Meta-analyses was conducted on the Pub Med and Web Science of Science until October 202...AIM:To assess the efficacy of ketotifen in treating allergic conjunctivitis.METHODS:A systematic search of systematic reviews and Meta-analyses was conducted on the Pub Med and Web Science of Science until October 2021 to address this knowledge gap.Mean difference with 95%CI and P values were used to assess the efficacy of ketotifen.The heterogeneity(I^(2))was used to evaluate the impact of heterogeneity.RESULTS:Eight randomized controlled trials(RCTs)involving 1589 patients were included in this Meta-analysis.The results revealed that after treating with ketotifen,itching(MD=-0.91,95%CI:-1.63 to-0.20,I^(2)=94%,P=0.01),tearing(MD=-0.40,95%CI:-0.61 to-0.18,I^(2)=75%,P=0.0003)and total signs and symptoms(MD=-0.85,95%CI:-1.12 to-0.58,I2=0,P<0.00001)showed better benefit effect compared to the placebo group.CONCLUSION:Topical ketotifen is an effective treatment for patients with allergic conjunctivitis.展开更多
AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old ...AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.CONCLUSION: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.展开更多
AIM: To demonstrate the effects of two different types of allergic conjunctivitis on severity of keratoconus (KC). ·METHODS: We retrospectively reviewed the medical records of 171 KC patients referred between Jun...AIM: To demonstrate the effects of two different types of allergic conjunctivitis on severity of keratoconus (KC). ·METHODS: We retrospectively reviewed the medical records of 171 KC patients referred between June 2010 and June 2011. The KC patients were divided into 3 groups as KC (group A), KC with vernal keratoconjunctivitis (VKC) (group B) and KC with allergic conjunctivitis (AC) (group C). Main outcome measures were demographic and ocular clinical features including age at presentation, gender, spherical equivalent (SE), best spectacle corrected visual acuity (BCVA), mean keratometric measurement (Km), central corneal thickness (CCT), and intraocular pressure (IOP). Groups were compared in term of study variables. · RESULTS: The median age at presentation was significantly lower in group B (P 【0.001). According to the median SE (P =0.003), BCVA(P =0.022), Km(P 【0.001), CCT (P =0.015) and Amsler-Krumeich classification (P 【 0.001), KC was more severe in group B. There was no significant difference in terms of IOP and corrected IOP among the groups (P =0.44), however there were 4 patients who had increased corrected IOP developed after topical corticosteroid use in group B. The differences among the groups persisted even after controlling for age and gender. · CONCLUSION: Our findings demonstrated a more severe KC in VKC patients despite their younger age which suggests evaluation of VKC patients as a separate group in keratoconus disease.展开更多
AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cyto...AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cytokines were detected.The mice were divided into 9 groups and the maslinic acid(MA)or PBS were given for different group after modeling.The expression levels of chemokine ligand 5(CCL5)and P-65 in the conjunctival tissue were analyzed by immunohistochemistry,quantitative reverse transcription polymerase chain reaction(q RT-PCR)and Western blot.The percentage of interleukin-17(IL-17)and CD4+CD25+in the splenocyte supernatant was analyzed by flow cytometry.Fur thermore,the serum and splenocyte supernatant concentration of total-IgE,interleukin-10(IL-10),and IL-17 was analyzed by enzyme linked immune response(ELISA).RESULTS:After the model was established,symptoms of conjunctivitis were alleviated,the level of P-65,CCL5,IL-17,and total-IgE was raised,while the expression of IL-10,CD4+CD25+was decreased.This result fully demonstrated that a typical IL-17/regulatory-T-cells(Treg cells)imbalance and NF-κB activation.When the NF-κB signal pathway was suppressed,it showed that there was a further relief of conjunctivitis in mice.At the same time,the expression of total-IgE,IL-17,and CCL5 was decreased and the expression of anti-inflammatory factor(IL-10,CD4+CD25+)was increased.CONCLUSION:In the state of immune tolerance,symptoms of conjunctivitis in mice are alleviated,the Th-17 cells of allergic conjunctivitis mice are inhibited,and Treg cells activity is enhanced.展开更多
Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,incl...Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,including 20 eyes without AC and 30 eyes with AC were enrolled in this study.All patients underwent a complete ocular examination,including evaluations of clinical manifestations of AC,corneal tomography and densitometry by Pentacam,corneal biomechanics by Corvis ST,and corneal and epithelial thickness mapping by RTvue optical coherence tomography(OCT).Results:The index of surface variance(ISV),index of vertical asymmetry(IVA),keratoconus index(KI),index of height decentration(IHD)and Belin/Ambrosio enhanced ectasia total deviation index(BAD-D)were significantly higher in the AC group than in the non-allergic conjunctivitis(NAC)group(P<0.05).The tomography and biomechanical index(TBl)was also significantly higher in the AC group(P=0.04).The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group(P<0.05).The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group(P<0.001).The ISV,IVA,KI,IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients(P<0.05).The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores(P<0.05).Conclusions:AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements,and the TBl could be used as an indicator of KC development risk in AC patients.Trial registration:Corneal Biomechanical Changes of Allergic Conjunctivitis,NCT04299399.Registered March 3,2020-Retrospectively registered.展开更多
Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,incl...Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,including 20 eyes without AC and 30 eyes with AC were enrolled in this study.All patients underwent a complete ocular examination,including evaluations of clinical manifestations of AC,corneal tomography and densitometry by Pentacam,corneal biomechanics by Corvis ST,and corneal and epithelial thickness mapping by RTvue optical coherence tomography(OCT).Results:The index of surface variance(ISV),index of vertical asymmetry(IVA),keratoconus index(KI),index of height decentration(IHD)and Belin/Ambrosio enhanced ectasia total deviation index(BAD-D)were significantly higher in the AC group than in the non-allergic conjunctivitis(NAC)group(P<0.05).The tomography and biomechanical index(TBI)was also significantly higher in the AC group(P=0.04).The average epithelial thickness in the 2-7mm annulus was significantly thinner in the AC group than in the NAC group(P<0.05).The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group(P<0.001).The ISV,IVA,KI,IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients(P<0.05).The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores(P<0.05).Conclusions:AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements,and the TBI could be used as an indicator of KC development risk in AC patients.展开更多
Background: Asthma exits with comorbidities which can affect the quality of life of children with asthma. Objective: To identify the common comorbidities with asthma, identify factors associated with the presence of s...Background: Asthma exits with comorbidities which can affect the quality of life of children with asthma. Objective: To identify the common comorbidities with asthma, identify factors associated with the presence of specific comorbidities and evaluate their impact on asthma severity and control among children attending the respiratory clinic in the Rivers State University Teaching Hospital. Materials & Methods: All asthma cases seen in the paediatric respiratory clinic, from 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;"> November 2014 to 30</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> October 2019 were consecutively recruited. Results: Of 264 children with asthma, 190 (72.0%) had other comorbidities with a F:M ratio of 1.56:1. Difficulty in breathing, chest pain, and the degree of asthma control w</span></span><span style="font-family:Verdana;">ere </span><span style="font-family:""><span style="font-family:Verdana;">significantly associated with having other comorbidities while SPO</span><sub><span style="font-family:Verdana;">2</span></sub><span style="font-family:Verdana;"> at 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;"> consult was significantly lower in children with comorbidities, P value</span></span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.05. Allergic rhinitis 116 (43.9%), adenotonsillar hypertrophy 99 (37.5%), atopic dermatitis 54 (20.5%), allergic conjunctivitis 37 (14%), food allergy 27 (10.2) and Gastroesophageal reflux14 (5.3%) were the commonest comorbidities identified. Majority </span><span style="font-family:Verdana;">(</span><span style="font-family:Verdana;">24</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">88.9%) had allergy to one type of food. Children < 3</span><span style="font-family:""> </span><span style="font-family:Verdana;">years and those whose age at diagnosis was <2</span><span style="font-family:""> </span><span style="font-family:Verdana;">years were significantly at lower risk of having atopic dermatitis. Gastroesophageal reflux disease was significantly more likely to be seen in children aged > 11</span><span style="font-family:""> </span><span style="font-family:Verdana;">years, overweight children, and those presenting with chest pain or chest tightness. Presence of various comorbidities increased the odds of having a more severe asthma, and likelihood of which increased with increasing number of coexisting comorbidities. Conclusion: The prevalence of allergic comorbidity is high among asthmatic children with allergic rhinitis being the commonest cause. Most children with asthma have more than one allergic comorbidity. A comprehensive evaluation of these comorbidities is thus essential in the management of asthmatic children for improved outcomes and quality of life.展开更多
文摘AIM:To assess the efficacy of ketotifen in treating allergic conjunctivitis.METHODS:A systematic search of systematic reviews and Meta-analyses was conducted on the Pub Med and Web Science of Science until October 2021 to address this knowledge gap.Mean difference with 95%CI and P values were used to assess the efficacy of ketotifen.The heterogeneity(I^(2))was used to evaluate the impact of heterogeneity.RESULTS:Eight randomized controlled trials(RCTs)involving 1589 patients were included in this Meta-analysis.The results revealed that after treating with ketotifen,itching(MD=-0.91,95%CI:-1.63 to-0.20,I^(2)=94%,P=0.01),tearing(MD=-0.40,95%CI:-0.61 to-0.18,I^(2)=75%,P=0.0003)and total signs and symptoms(MD=-0.85,95%CI:-1.12 to-0.58,I2=0,P<0.00001)showed better benefit effect compared to the placebo group.CONCLUSION:Topical ketotifen is an effective treatment for patients with allergic conjunctivitis.
基金A grant-in-aid for Scientific Research from the Japanese Ministry of Education,Culture,Sports,Science and Technology
文摘AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.CONCLUSION: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.
文摘AIM: To demonstrate the effects of two different types of allergic conjunctivitis on severity of keratoconus (KC). ·METHODS: We retrospectively reviewed the medical records of 171 KC patients referred between June 2010 and June 2011. The KC patients were divided into 3 groups as KC (group A), KC with vernal keratoconjunctivitis (VKC) (group B) and KC with allergic conjunctivitis (AC) (group C). Main outcome measures were demographic and ocular clinical features including age at presentation, gender, spherical equivalent (SE), best spectacle corrected visual acuity (BCVA), mean keratometric measurement (Km), central corneal thickness (CCT), and intraocular pressure (IOP). Groups were compared in term of study variables. · RESULTS: The median age at presentation was significantly lower in group B (P 【0.001). According to the median SE (P =0.003), BCVA(P =0.022), Km(P 【0.001), CCT (P =0.015) and Amsler-Krumeich classification (P 【 0.001), KC was more severe in group B. There was no significant difference in terms of IOP and corrected IOP among the groups (P =0.44), however there were 4 patients who had increased corrected IOP developed after topical corticosteroid use in group B. The differences among the groups persisted even after controlling for age and gender. · CONCLUSION: Our findings demonstrated a more severe KC in VKC patients despite their younger age which suggests evaluation of VKC patients as a separate group in keratoconus disease.
基金Supported by the Provincial Innovation Team for Cataract and Ocular Fundus Disease in the Second People’s Hospital of Yunnan Province(No.2017HC010)the Key Laboratory of Yunnan Province for the Prevention and Treatment of Ophthalmology(No.2017DG008)Expert Workstation of Yao Ke(No.2017IC064)。
文摘AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cytokines were detected.The mice were divided into 9 groups and the maslinic acid(MA)or PBS were given for different group after modeling.The expression levels of chemokine ligand 5(CCL5)and P-65 in the conjunctival tissue were analyzed by immunohistochemistry,quantitative reverse transcription polymerase chain reaction(q RT-PCR)and Western blot.The percentage of interleukin-17(IL-17)and CD4+CD25+in the splenocyte supernatant was analyzed by flow cytometry.Fur thermore,the serum and splenocyte supernatant concentration of total-IgE,interleukin-10(IL-10),and IL-17 was analyzed by enzyme linked immune response(ELISA).RESULTS:After the model was established,symptoms of conjunctivitis were alleviated,the level of P-65,CCL5,IL-17,and total-IgE was raised,while the expression of IL-10,CD4+CD25+was decreased.This result fully demonstrated that a typical IL-17/regulatory-T-cells(Treg cells)imbalance and NF-κB activation.When the NF-κB signal pathway was suppressed,it showed that there was a further relief of conjunctivitis in mice.At the same time,the expression of total-IgE,IL-17,and CCL5 was decreased and the expression of anti-inflammatory factor(IL-10,CD4+CD25+)was increased.CONCLUSION:In the state of immune tolerance,symptoms of conjunctivitis in mice are alleviated,the Th-17 cells of allergic conjunctivitis mice are inhibited,and Treg cells activity is enhanced.
基金supported by the Key Area Research and Development Program of Guangdong Province(Grant No.2019B010152001)the National Natural Science Foundation of China(Grant No.81670826).
文摘Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,including 20 eyes without AC and 30 eyes with AC were enrolled in this study.All patients underwent a complete ocular examination,including evaluations of clinical manifestations of AC,corneal tomography and densitometry by Pentacam,corneal biomechanics by Corvis ST,and corneal and epithelial thickness mapping by RTvue optical coherence tomography(OCT).Results:The index of surface variance(ISV),index of vertical asymmetry(IVA),keratoconus index(KI),index of height decentration(IHD)and Belin/Ambrosio enhanced ectasia total deviation index(BAD-D)were significantly higher in the AC group than in the non-allergic conjunctivitis(NAC)group(P<0.05).The tomography and biomechanical index(TBl)was also significantly higher in the AC group(P=0.04).The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group(P<0.05).The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group(P<0.001).The ISV,IVA,KI,IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients(P<0.05).The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores(P<0.05).Conclusions:AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements,and the TBl could be used as an indicator of KC development risk in AC patients.Trial registration:Corneal Biomechanical Changes of Allergic Conjunctivitis,NCT04299399.Registered March 3,2020-Retrospectively registered.
基金supported by grants from the Key Area Research and Development Program of Guangdong Province(No.2019B010152001)the National Natural Science Foundation of China(81670826).
文摘Background:To explore corneal biomechanical changes,identify related factors and determine early indicators of keratoconus(KC)development risk in allergic conjunctivitis(AC)patients.Methods:A total of 50 patients,including 20 eyes without AC and 30 eyes with AC were enrolled in this study.All patients underwent a complete ocular examination,including evaluations of clinical manifestations of AC,corneal tomography and densitometry by Pentacam,corneal biomechanics by Corvis ST,and corneal and epithelial thickness mapping by RTvue optical coherence tomography(OCT).Results:The index of surface variance(ISV),index of vertical asymmetry(IVA),keratoconus index(KI),index of height decentration(IHD)and Belin/Ambrosio enhanced ectasia total deviation index(BAD-D)were significantly higher in the AC group than in the non-allergic conjunctivitis(NAC)group(P<0.05).The tomography and biomechanical index(TBI)was also significantly higher in the AC group(P=0.04).The average epithelial thickness in the 2-7mm annulus was significantly thinner in the AC group than in the NAC group(P<0.05).The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group(P<0.001).The ISV,IVA,KI,IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients(P<0.05).The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores(P<0.05).Conclusions:AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements,and the TBI could be used as an indicator of KC development risk in AC patients.
文摘Background: Asthma exits with comorbidities which can affect the quality of life of children with asthma. Objective: To identify the common comorbidities with asthma, identify factors associated with the presence of specific comorbidities and evaluate their impact on asthma severity and control among children attending the respiratory clinic in the Rivers State University Teaching Hospital. Materials & Methods: All asthma cases seen in the paediatric respiratory clinic, from 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;"> November 2014 to 30</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> October 2019 were consecutively recruited. Results: Of 264 children with asthma, 190 (72.0%) had other comorbidities with a F:M ratio of 1.56:1. Difficulty in breathing, chest pain, and the degree of asthma control w</span></span><span style="font-family:Verdana;">ere </span><span style="font-family:""><span style="font-family:Verdana;">significantly associated with having other comorbidities while SPO</span><sub><span style="font-family:Verdana;">2</span></sub><span style="font-family:Verdana;"> at 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;"> consult was significantly lower in children with comorbidities, P value</span></span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.05. Allergic rhinitis 116 (43.9%), adenotonsillar hypertrophy 99 (37.5%), atopic dermatitis 54 (20.5%), allergic conjunctivitis 37 (14%), food allergy 27 (10.2) and Gastroesophageal reflux14 (5.3%) were the commonest comorbidities identified. Majority </span><span style="font-family:Verdana;">(</span><span style="font-family:Verdana;">24</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">88.9%) had allergy to one type of food. Children < 3</span><span style="font-family:""> </span><span style="font-family:Verdana;">years and those whose age at diagnosis was <2</span><span style="font-family:""> </span><span style="font-family:Verdana;">years were significantly at lower risk of having atopic dermatitis. Gastroesophageal reflux disease was significantly more likely to be seen in children aged > 11</span><span style="font-family:""> </span><span style="font-family:Verdana;">years, overweight children, and those presenting with chest pain or chest tightness. Presence of various comorbidities increased the odds of having a more severe asthma, and likelihood of which increased with increasing number of coexisting comorbidities. Conclusion: The prevalence of allergic comorbidity is high among asthmatic children with allergic rhinitis being the commonest cause. Most children with asthma have more than one allergic comorbidity. A comprehensive evaluation of these comorbidities is thus essential in the management of asthmatic children for improved outcomes and quality of life.