| Background and ObjectiveRifampicin-resistant tuberculosis（RR-PTB）refers to Mycobacterium Tuberculosis that is resistant to Rifampicin and covers all rifampicin-resistant tuberculosis（TB）.RR-PTB is highly infectious and has a low cure rate,posing a serious threat to public health.In addition,due to its extremely long course and high cost,treatment adherence in patients with RR-PTB is generally low.Previous studies have shown that the treatment adherence of TB patients is an important factor affecting the treatment effect,while currently there are more studies on the treatment adherence of common tuberculosis,and relatively few studies on the influencing factors of RR-PTB adherence.Therefore,in the first part,we aimed to understand the current status of the treatment and management of RR-PTB patients in Anhui province,and analyze the factors affecting the treatment adherence of RR-PTB patients.Based on the results of the first part of the study,income is an important factor influencing adherence,and the free drug policy can alleviate the pressure of TB patients not adhering to treatment due to low income.As the free distribution of second-line anti-TB drugs continues in Anhui province,its effectiveness remains unknown.Studies have shown that psychological emotions can affect treatment adherence,treatment outcomes and quality of life.We speculate that the free distribution of second-line anti-TB drugs may influence treatment outcomes by affecting patients’psychological and emotional well-being.Therefore,in the second part,we studied the influence of free distribution of second-line anti-tuberculosis drugs in Anhui Province on the psychological state of patients with RR-PTB,determined the characteristics of the population to be provided with free drugs,built a prediction model based on trial results and drew a Nomogram to predict whether the characteristic individuals should be provided with free drugs.Therefore,this study intends to conduct a two-part investigation in order to reveal the main influencing factors of the treatment adherence of RR-PTB,explore the influence of free drugs on the psychological state of patients,determine the characteristics of the population dispensing free drugs,and quantify the probability of dispensing free drugs for specific individuals in the future.To provide a scientific basis for improving the treatment adherence of RR-PTB patients and improving the distribution of free second-line anti-tuberculosis drugs in Anhui Province.MethodsThis study was divided into two parts.The first part used a cross-sectional design and the second part used intervention research.A sampling survey of RR-PTB patients in 16 prefecture-level cities in Anhui Province was conducted by combining quantitative and qualitative research methods.In the first part,based on the data of TB registration and management information system,the distribution of RR-PTB in Anhui Province was mastered and the sampling method was determined.Subsequently,201 cases of RR-PTB patients registered in Anhui Province from January 1,2017 to December 31,2017 were identified by stratified cluster sampling according to certain inclusion and exclusion criteria.TB doctors in designated hospitals designed a questionnaire for treatment adherence of RR-PTB based on clinical experience,qualitative research results,and reference to previous literature reports.201 patients with RR-PTB were investigated by self-designed structured questionnaire.The main contents included:Basic sociodemographic characteristics,knowledge related to RR-PTB,current status of treatment management,treatment adherence（patients who can adhere to regular medication,regular review during the entire RR-PTB treatment,and no interruption of treatment at the end of the survey were defined by doctors as compliant,otherwise defined as non-compliant）and its influencing factors.In the second part,cluster sampling method was adopted,which was divided into two groups according to whether free drugs were distributed or not:free drugs group and no free drugs group.Since RR-PTB patients were treated for up to 24 months,patients diagnosed in 2020 were still hospitalized during the survey period,and there was a need for authenticity based on face-to-face questionnaires.Therefore,combined with the sample survey of RR-PTB patients registered from January 1,2021 to December 31,2021 in the trial area of dispensing free drugs,a total of 89 cases were selected from the two groups,including 49 cases in the group of dispensing free drugs and 40 cases in the group of not dispensing free drugs.A self-made questionnaire was used to investigate the two groups of RR-PTB patients.The main contents included:basic sociodemographic characteristics,combination therapy,free medication,general health questionnaire（GHQ-12）,mental resilience level（CD-RISC）,self-rating anxiety scale and self-rating depression scale.Epidata 3.1 software was used for questionnaire entry,SPSS 22.0 software and R4.2.0 software were used for statistical analysis.Descriptive statistical analysis,chi-square test and binary logistic regression were used to analyze the influencing factors of treatment adherence of RR-PTB.Mann-Whitney U test was used to analyze the differences in the scores of general health questionnaire（GHQ-12）,mental resilience level（CD-RISC）,self-rating anxiety scale and self-rating depression scale between the two groups.Multivariate logistic regression was used to analyze the differences in the characteristics of the two groups with or without free drugs,and to determine the characteristics of the groups with free drugs.The prediction model is constructed and the Nomo prediction chart for the distribution of free drugs is drawn.The area under the curve（AUC）of the subject was calculated and the accuracy of the prediction model was evaluated by sensitivity and specificity.Then,Clinical impact curve（CIC）was drawn to determine the authenticity and threshold probability of the prediction model,and Decision Curve Analysis（DCA）was used to evaluate the clinical availability and benefit of the prediction model.ResultsIn the first part,according to the data of TB registration and management information system,291,334 and 511 cases of RR-PTB were found in Anhui Province in 2016,2017 and 2018,respectively,and the number of patients in northern Anhui was higher than that in southern Anhui in three years.In the investigation of influencing factors of adherence,a total of 201 cases of RR-PTB patients who were not given free drugs were investigated,with a sex ratio of 2.9:1,an average age of 50.5±16.4 years old,86.1%with a high school or secondary technical school education below,22.7%of the occupation distribution were farmers,21.1%were unemployed in housework,and 18.0%were migrant workers.97.5%of the patients had medical insurance,45.8%lived in urban areas,37.8%in rural areas,and 57.3%of the patients had a family size of 2-3 people.72.6%of patients had good treatment adherence,and only 16.9%of RR-PTB patients knew relevant disease knowledge.The qualitative study found age differences among those who improved after a short period of antituberculosis therapy,with strong adverse reactions as risk factors for"poor adherence"and who received free drugs or not.Univariate analysis showed that education level（χ2=12.898,P=0.002）,place of residence（χ2=11.220,P=0.004）,monthly family income（χ2=18.401,P=0.001）,and the presence of other chronic diseases（χ2=7.174,P=0.007）and the number of previous anti-tuberculosis treatments（χ2=18.049,P=0.001）were the influencing factors of treatment adherence.Theχ2 test found that there were significant differences between primary school and junior high school,junior college and above.There are statistical differences among cities,counties and rural areas.The monthly household income of2000 yuan or less is statistically different from that of 2001 to 5000 yuan or more than5000 yuan.There was statistical difference between the first and second anti-tuberculosis treatment and the second or more treatment.Binary logistic regression showed that patients with monthly family income of 2000-5000 yuan（with less than2000 yuan as reference）had good treatment adherence（OR=2.810,95%CI:1.210-6.720）.The second part found that the score of CD-RISC scale in the intervention group was higher than that in the non-intervention group（M0=65,M1=71）,and the difference between the two groups was statistically significant（U=717.00,P=0.030）.Age was included in the univariate logistic regression model,and it was found that the younger patients were more likely to receive free drugs（OR=0.962,95%CI:0.932-0.990）.The area under the Receiver operating characteristic curve（ROC）was 0.666（95%CI:0.554-0.778）.The results of collinearity diagnosis showed that VIF of 10 factors that may affect the distribution of free drugs by TB clinicians in designated hospitals in the trial process were all near 3,and there was no collinearity.Multivariate logistic regression found that TB clinicians in designated hospitals targeted older RR-PTB patients（OR=0.928,P=0.003）,Elementary school culture（OR=0.011,P=0.003）,middle school culture（OR=0.059,P=0.019）,high school or technical secondary school culture（OR=0.017,P=0.004）,and junior college culture（OR=0.025,P=0.015）were less likely to distribute free drugs than illiterate patients.TB clinicians in designated hospitals were more likely to distribute free drugs to poor households（OR=39.225,P=0.000）.A prediction model is constructed according to age,education level,poverty or not.The area under ROC curve of the prediction model is 0.841（95%CI:0.760-0.923）.At this point,the sensitivity and specificity calculated based on"closest.Delong test found that there was a statistical difference in the AUC area under the two ROC curves（Z=-2.964,P=0.003）,so the prediction model built by age,education level and poor households had good accuracy.The clinical impact curve further verified the authenticity of the prediction model constructed by age,education level and poor households,and determined that the threshold probability of this prediction model was 0.6.When the total predicted probability of RR-PTB individuals exceeds the critical value of 0.6,the number of people predicted to be given free drugs coincides with the number of people actually given free drugs.The analysis of decision curve showed that when threshold probability>0.2,the net benefit of multivariate complex model（including age,education level,whether poor households or not）was greater than that of univariate simple model（including age only）,free medication for the whole population and no implementation of free medication.Nomogram drawn according to prediction model has good clinical practicability and benefit.ConclusionsThis study found that the treatment adherence of RR-PTB patients in Anhui province was poor,and the awareness rate of RR-PTB related knowledge was low,which should be paid high attention to.In particular,treatment adherence should be improved for patients with primary school education or below,non-urban residents,monthly household income of 2000 yuan or less,complicated with other chronic diseases,and who have received anti-tuberculosis treatment twice or more in the past.The mental resilience level of patients who enjoy free drugs was better than that of those who did not enjoy free drugs,and the characteristics of patients who enjoy free drugs were young patients,illiterate patients and patients from poor families.The prediction model had good clinical practicability and accuracy.The Nomo plot based on the prediction model had maintained excellent net benefit at threshold probability>0.2,so it can be used as a reference for future clinical distribution of free drugs.In the future,the distribution of free second-line anti-TB drugs should focus on patients with a total predicted probability of>0.6,so as to maximize the benefits of free distribution of second-line anti-TB drugs under the condition of limited government funding. |
