Monthly Archives: August 2022

Introduction

Chronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by persistent airflow limitation.1 Over the past few decades, the morbidity and mortality of COPD has increased exponentially, affecting the global About 384 million people, it is now considered the third leading cause of death globally.2 Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is defined as an acute worsening of respiratory symptoms that require additional treatment, with significant negative impact on health status, hospitalization, readmission, disease progression, and mortality. It not only seriously affects the quality of life of patients, but also imposes a heavy economic burden on families, medical systems and society.3,4

Non-invasive ventilation (NIV) is the preferred initial mode of ventilator assistance for patients with acute hypercapnic breathing failure caused by AECOPD.5,6 Compared with invasive mechanical ventilation (IMV), AECOPD patients treated with NIV has lower in-hospital mortality, shorter hospital stay and lower cost.7,8 With the development of medicine, invasive-noninvasive sequential ventilation strategy has become an effective way to wean off invasive mechanical ventilation in patients with AECOPD. And it has significantly reduced weaning-related mortality, pneumonia and ventilation time.9

High Flow Nasal Cannula (HFNC) is a new type of non-invasive breathing assistance method that can improve ventilation and oxygen by providing precise oxygen concentration heated and humidified oxygen, better tolerance and comfort than NIV.10 It may reduce the volume of dead space and increase the alveolar volume, which can result in improvement of alveolar ventilation and gas exchange.11 For COPD patients with type II respiratory failure and pH between 7.25 and 7.35, HFNC was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2h of treatment in patients with mild-to-moderate AECOPD.12 A recent meta-analysis study showed that HFNC is more beneficial than NIV in the treatment of COPD and hypercapnic respiratory failure.13 However, in the process of weaning of AECOPD patients, the therapeutic effect of HFNC and whether it can be used as an alternative therapy for NIV is still unclear. Therefore, in this study, the method of meta-analysis was used to analyze the therapeutic effect of HFNC and NIV in patients with AECOPD after extubation, in order to provide evidence-based basis for clinical practice.

This systematic review and meta-analysis was registered at PROSPERO (http://www.crd.york.ac.uk/prospero, CRD:42022312973) and designed as per the Cochrane Handbook for Systematic Reviews of Interventions14 and reported according to the PRISMA guidelines.15

Retrieval database: PubMed, Web of science, Embase, Cochrane Library database. Retrieval database date is from establishment to March 10, 2022. Retrieval combines subject headings and free words: Pulmonary Disease, Chronic Obstructive, High-Flow Nasal Cannula OR HFNC OR High-Flow Oxygen Therapy OR High-Flow nasal oxygen OR High nasal flow OR High-Flow nasal cannula oxygen therapy OR High-Flow oxygen, Noninvasive ventilation. For detailed search strategies, see in Supplementary Data S1.

Inclusion criteria were as follows:(1) adults 18 years old,(2) Patients who meet the diagnostic criteria of COPD, have acute exacerbation and receive invasive intubation,(3) comparison of the effects of HFNC and NIV as the key study objective,(4) RCT study design,(5) at least one data outcome of interest available for extraction,(6) Chinese and English literature. Exclusion criteria are:(1) patients under the age of 18,(2) non-RCT studies,(3) data are incomplete or cannot be extracted,(4) full text is not available.

Our purpose is to evaluate the effect of HFNC and NIV on the prognosis of AECOPD patients after extubation, Therefore, the primary outcome indicator we selected is: reintubation rate. Secondary outcomes included: mortality, complication rate, and ICU length of stay, respiratory rate(RR), heart rate(HR), pH, oxygenation index (PaO2/FiO2), and partial pressure of carbon dioxide (PaCO2).

Literature screening we imported the retrieved literature into the ENDNOTE software, and two researchers independently reviewed each retrieved document, according to the inclusion and exclusion criteria, preliminary screening of the documents by reading the title and abstract, and then preliminary screening by reading the full text. Filter the file for further filtering. For trials that met the inclusion criteria, we extracted basic information from the articles, such as the first authors last name, year of publication, participant type, sample size, intervention, control and outcome. As for quality assessment, the quality of RCTs was assessed using the Cochrane risk of bias tool, including assessment of random sequence generation, allocation concealment, patient and intervention blinding, outcome measurer blinded, incomplete outcome data, selective reporting, and other potential biases. Each item was rated as low risk,high risk or unclear, and the evaluation was conducted independently by two authors. Disagreements were resolved through arbitration by discussion and consultation with a third author.

As for statistical analysis, all analyses were performed using STATA SE 15.1, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD), and each effect size was represented by 95% confidence interval (CI). The heterogeneity among the results of the included studies was analyzed by the I2 test. P<0.05 was considered to be statistically significant. When the heterogeneity test P 0.05 and I2<50%, multiple similar studies were considered to have homogeneity. If P<0.05 and I2 50%, a random-effects model was used. If multiple time points were reported for the outcome measure, we selected the common time point included in most experiments. Mean and SD values were estimated when outcome measures were reported as interquartile range and median range (or 95% confidence interval). The Engauge Digitizer (version 4.1) graphical data extraction software was used to extract data that were only provided by images. Funnel plots and Egger tests were not used to assess potential publication bias because the number of studies performed for quantitative analysis was <10, in which case funnel plots and Egger tests could produce misleading results.16 Sensitivity analysis was performed on the necessary outcome indicators to determine the stability of the results.

We performed a subgroup analysis based on baseline PaCO2 levels. We believe that the average PaCO2 50 mmHg at the beginning of the trial or patients with type II respiratory failure were included in the study has hypercapnia, while the lower baseline PaCO2< 50 mmHg at the beginning of the trial has no hypercapnia.

A total of 710 relevant studies were initially detected, and after reading the literature titles and abstracts, they were screened according to the inclusion and exclusion criteria, and 8 qualified clinical studies were finally included,1724 a total of 612 subjects. There were 297 subjects in the HFNC group and 315 subjects in the NIV group. The screening process is shown in Figure 1, and the basic characteristics of the included studies are shown in Table 1.

Table 1 Characteristics of Included Studies

Figure 1 PRISMA (preferred reporting items for systematic reviews and meta-analysis) flow diagram.

Notes: Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:160. Creative Commons.15

In the 8 RCT studies included,4 were in Chinese17,18,20,23 and 4 were in English.19,21,22,24 8 studies explicitly mentioned the method of generating random sequences, among which there are 4 items that mention allocation hiding. Due to differences in oxygen therapy equipment, it was difficult to blind study patients and interventionists. No other risk of bias was found in all findings. Details are shown in Supplementary Figure S2.

All of the eight studies1724 reported the effect of HFNC on the reintubation rate of AECOPD patients after extubation, there are six studies1720,22,24 observed reintubation rate within 3 days and two studies21,23 observed within 7 days (Figure 2), the heterogeneity test result was I2=27.7%, P=0.207, using a fixed effect model, the results showed RR (1.49 [95% CI,0.95 to 2.33], P=0.082), the difference was not statistically significant. Subgroup analysis was performed according to whether the included population was accompanied by hypercapnia. In the hypercapnia group, the heterogeneity test result was I2=0.00%, P=0.602, and the results showed RR (0.69 [95% CI,0.33 to 1.44], P=0.317), the difference was not statistically significant. It shows that compared with NIV, HFNC has no statistical difference in the reintubation rate of patients with AECOPD, and the two treatment effects are equivalent. In the non-hypercapnia group, the heterogeneity test result was I2=0.00%, P=0.420, the results showed RR (2.61 [95% CI,1.41 to 4.83], P=0.002), the difference was statistically significant, indicating that the reintubation rate of the HFNC group was higher, and the treatment effect was not as good as that of the NIV group.

Figure 2 Forest plot of reintubation rates, subgroup analysis was performed according to variable of hypercapnia and non-hypercapnia.

Seven studies1721,23,24 reported the effect of HFNC on the mortality of AECOPD patients after extubation, four17,19,20,24 of them reported 28 day mortality and three18,21,23 of them reported mortality during hospitalization (Figure 3), the test result of the heterogeneity was I2=0.0%, P=0.939, using a fixed effect model, the results showed RR (0.92 [95% CI,0.56 to 1.52] P=0.752), the difference was not statistically significant. In subgroup analysis, with hypercapnia RR (1.09 [95% CI,0.55 to 2.14], P = 0.813), the difference was not statistically significant, without hypercapnia RR (0.77 [95% CI,0.37 to 1.61], P = 0.492), the difference was not statistically significant. It showed that there was no statistical difference between HFNC and NIV on the mortality of AECOPD patients regardless of whether it was accompanied by hypercapnia.

Figure 3 Forest plot of mortality, subgroup analysis was performed according to variable of hypercapnia and non-hypercapnia.

Six studies1719,21,23,24 reported the effect of HFNC and NIV on the ICU length of stay in days in patients with AECOPD after extubation (Figure 4), the heterogeneity test result was I2=87.4%, P= 0.00, using a random effects model, the results showed that MD (0.44 [95% CI,-1.01 to 0.13], P=0.132), the difference was not statistically significant. In subgroup analysis, there was no statistically significant difference in MD with hypercapnia (0.23 [95% CI,-0.51 to 0.05], P = 0.102), and without hypercapnia (0.74 [95% CI,-2.16 to 0.69], P = 0.313).

Figure 4 Forest plot of ICU length of stay, subgroup analysis was performed according to variable of hypercapnia and non-hypercapnia.

Six studies1719,2224 reported the effect of HFNC and NIV on the complication rate of AECOPD patients after extubation, Complications mainly include nasal facial skin breakdown and aspiration and flatulence during the treatment, no serious adverse events were reported (Figure 5), the heterogeneity test result was I2=1.9%, P =0.404, using a fixed effect model, the results showed RR (0.22 [95% CI,0.13 to 0.39], P=0.00), the difference was statistically significant. In subgroup analysis, with hypercapnia RR (0.24 [95% CI,0.13 to 0.43], P = 0.000)was statistically significant, and non hypercapnia RR (0.18 [95% CI,0.04 to 0.75], P = 0.018), the difference was statistically significant. Compared with NIV, it indicated that HFNC could significantly reduce the complications of post-extubation patients.

Figure 5 Forest plot of complication rates, subgroup analysis was performed according to variable of hypercapnia and non-hypercapnia.

The following data of all outcome indicators are selected from all studies with a total time of 24 hours. Seven studies1720,2224 reported the effect of HFNC and NIV on PaCO2 in patients with AECOPD after extubation. The results of heterogeneity test were I2=91.1%, P=0.00, using Random effects model, the results showed that MD (0.19 [95% CI,-0.84 to 0.45], P=0.561), the difference was not statistically significant. In subgroup analysis, there was no significant difference in MD (0.37 [95% CI,-1.21 to 0.46], P=0.378) with hypercapnia, and MD (0.28 [95% CI,-0.14 to 0.70], P=0.186) without hypercapnia. Four studies18,19,23,24 reported the effect of HFNC and NIV on the heart rate of AECOPD patients after extubation. The results of the heterogeneity test were I2=69.2%, P=0.021, using a random effect model, the results showed that MD (0.38 [95% CI,-0.85 to 0.09], P=0.115), the difference was not statistically significant. In subgroup analysis, there was no significant difference in MD (0.42 [95% CI,-1.05 to 0.21], P=0.191)with hypercapnia, without hypercapnia MD (0.24 [95% CI,-0.83 to 0.36], P=0.435), the difference was not statistically significant. Five studies18,19,2224 reported the effect of HFNC and NIV on the respiratory rate of AECOPD patients after extubation. The results of heterogeneity test were I2=20%, P=0.288, using a fixed effect model, the results showed that MD (0.51 [95% CI,-0.73 to 0.30], P=0.000), the difference was statistically significant. Subgroup analysis was performed, with hypercapnia MD (0.58 (95% CI,-0.81 to 0.35), P=0.000), the difference was statistically significant, without hypercapnia MD (0.07 [95% CI,-0.67 to 0.52], P=0.807), the difference was not statistically significant. It indicated that HFNC significantly reduced the respiratory rate in AECOPD patients with hypercapnia, but in AECOPD patients without hypercapnia, the difference was not statistically significant and the treatment effect is equivalent. Four studies18,19,23,24 reported the effect of HFNC and NIV on the acid-base balance of patients with AECOPD after extubation. The results of the heterogeneity test were I2=81.7%, P=0.001, using a random effect model, the results showed that MD (0.37 [95% CI,-0.25 to 0.98], P=0.24), the difference was not statistically significant. Subgroup analysis was performed, with hypercapnia MD (0.52 [95% CI,-0.26 to 1.30], P=0.191), the difference was not statistically significant, without hypercapnia MD (0.10 [95% CI,-0.69 to 0.49], P=0.739), the difference was not statistically significant. Five studies1719,22,24 reported the effect of HFNC and NIV on PaO2/FiO2 in patients with AECOPD after extubation. The results of heterogeneity test were I2=71.0%, P=0.008, using random effects model, the results showed MD (0.14 [95% CI,-0.27 to 0.54], P=0.514), the difference was not statistically significant. Subgroup analysis was performed, with hypercapnia MD (0.30 [95% CI,-0.05 to 0.64], P=0.093), the difference was not statistically significant, without hypercapnia MD (0.55 [95% CI,-1.15 to 0.05], P=0.070), the difference was not statistically significant. (See in Table 2, Supplementary Figure S3 for detailed forest diagrams.)

Table 2 Other Outcome Measures

We performed subgroup analyses for all outcomes, most of which showed good homogeneity, and we performed sensitivity analyses for outcomes with higher heterogeneity, sensitivity analysis was performed to exclude studies one by one, all the results remained unchanged (see in Supplementary Figure S4).

Mechanical ventilation is widely used in the treatment of respiratory failure caused by various reasons, and is of great significance in the clinical treatment of chronic obstructive pulmonary disease. The difficulty of weaning patients with acute exacerbation of chronic obstructive pulmonary disease is one of the important clinical problems, The reasons were ventilator fatigue and worsening respiratory mechanics.25 NIV can supply stable high-concentration oxygen, relaunched alveoli, improve gas exchange, and reduce intubation and mortality in patients with respiratory failure, especially those with exacerbated chronic obstructive pulmonary disease. However, NIV can lead to many complications, such as skin damage, eye irritation, claustrophobia, dryness of the oropharynx, flatulence, aspiration and expectoration difficulties, and affects eating and communication, resulting in poor tolerance and comfort, and extremely greatly limit its clinical application.26,27 HFNC can provide high-flow gas to patients, and HFNC can generate positive airway pressure, increase functional residual capacity, improve oxygenation,28 and allow patients to receive a constant oxygen concentration.29 Heated and humidified gas can promote airway secretions It can clear the airway, protect airway epithelial cells, and reduce the discomfort of patients.30

In this study, we mainly compared the reintubation rate of HFNC and NIV in the post-extubation treatment of AECOPD patients, this is different from previous systematic reviews, even the seven included studies were in the last 3 years. The results of reintubation rate showed that there was no statistical difference between them, Subgroup analysis was conducted between hypercapnia and non-hypercapnia, and the results showed that there was no significant difference in patients with hypercapnia, but in patients without hypercapnia, the reintubation rate in HFNC group was significantly higher than the NIV group, This result suggests that the effect of HFNC in AECOPD patients with hypercapnia is similar to NIV, which may be related to the reduction of respiratory muscle load and respiratory overwork by both of them, which is consistent with the results of previous studies.12,31,32 It can be used as an alternative treatment for NIV after extubation in AECOPD patients with hypercapnia, and has certain advantages, but in AECOPD patients without hypercapnia, the treatment effect of HFNC is not as good as NIV, It may be related to the lower respiratory pressure provided by HFNC than NIV. Although all included studies have given the judgment criteria for failure of HFNC or NIV treatment, mainly focusing on the patients respiratory rate, blood gas analysis, consciousness status and clinicians decision-making, the judgment criteria are different, and there are risks of delayed intubation and increased complications. In future studies, if an effective standard, such as Rox or mrox or hacor3336 can be used, the results will be more reliable.

In the analysis of complication rates, HFNC was significantly lower than NIV, and there was no change in the results of subgroup analysis, which may be related to NIV and the intolerance to the interface and poor patientventilator interaction and Synchronization.37,38 In the analysis of respiratory rate, compared with NIV, HFNC can reduce the respiratory rate of patients with AECOPD after extubation, and the subgroup analysis results suggest that HFNC has a strong effect on reducing respiratory rate in AECOPD with hypercapnia, in AECOPD patients without hypercapnia, its performance was not statistically different from NIV. The reason for the analysis may be that the long-term airflow limitation in AECOPD patients will lead to increased diaphragm load, resulting in diaphragm injury and diaphragm fatigue, which is not conducive to Patient breathing.39 HFNC can provide heated and humidified oxygen, sufficient oxygen flow and positive end-expiratory pressure, which can limit the inflammatory response and bronchial epithelial cell damage, reduce the bodys hyperresponsiveness or irritation, promote the improvement of the airway, and effectively flush the airway, promote the recovery of respiratory ciliary function, effectively remove excess carbon dioxide in the body, promote pulmonary gas exchange, improve oxygen utilization, improve patient ventilation function, and reduce respiratory power consumption, thereby helping to improve diaphragm fatigue and reduce diaphragm damage.4043 In the analysis of mortality, ICU length of stay, PaCO2, pH, HR, PaO2/FiO2, there was no statistical difference between HFNC and NIV, showing the treatment effect is equivalent.

Recent studies have shown that compared with HFNC alone, extubation Immediately applied HFNC plus NIV significantly reduced the risk of reintubation and post-extubation respiratory failure in patients at high risk of extubation failure.44 The result may provide further insight into the choice of respiratory support methods after extubation, and provide a possibility for the combined and alternate application of HFNC and NIV in the future.

In general, According to the available evidence, the application of HFNC can be used as a treatment option for AECOPD patients with hypercapnia. It has certain advantages as an alternative to NIV after extubation, but in AECOPD patients without hypercapnia, HFNC is not as effective as NIV, the result needs further evaluation.

The limitations of this study are as follows: firstly, the number of included studies is relatively small, with a total of 8 articles involving 612 subjects (297 in the HFNC group and 315 in the NIV group). secondly, the quality of the included studies is generally not high. Because of differences in oxygen therapy equipment, it is difficult to blind study patients and interventionists, which may affect the estimation of outcome measures. Thirdly, all included studies have given the judgment criteria for failure of HFNC or NIV treatment are different, may affect the results. Fourthly, a total of 8 studies included, seven of which are from China, may have regional differences and cannot be used as evidence of globalization. High-quality, multi-center RCT studies worldwide are still needed to further evaluate the effect of HFNC in patients after extubation of AECOPD. In conclusion, the results of the study should be interpreted with caution.

According to the Meta-analysis results of the existing evidence, the application of HFNC can be used as an alternative treatment for NIV after extubation in AECOPD patients with hypercapnia, and there are certain advantages, but whether HFNC can be used as an alternative treatment for NIV in AECOPD patients without hypercapnia after extubation still needs to be further studied. In the future, more high-quality, multicenter RCT studies are still needed to further verify the effect of HFNC in patients after extubation of AECOPD.

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All authors have made significant contributions to the work of the report, whether in terms of concept, research design, implementation, data acquisition, analysis and interpretation, or in all these areas; Participate in the drafting, modification or critical review of the clause; Final approval of the forthcoming edition; An agreement has been reached on the journal to submit the article; And agree to be responsible for all aspects of the work.

There is no funding to report.

The authors report no conflicts of interest in this work.

1. Vogelmeier CF, Criner GJ, Martinez FJ., et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017;195(5):557582. doi:10.1164/rccm.201701-0218PP

2. Augusti A, Beasley R, Celli BR, et al. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnoses, management, and prevention of COPD; 2020. Available from: http://www.goldcopd.org. Accessed May 27, 2021.

3. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7(7):CD004104. doi:10.1002/14651858.CD004104.pub4

4. Kunadharaju R, Sethi S. Treatment of acute exacerbations in chronic obstructive pulmonary disease. Clin Chest Med. 2020;41(3):439451. doi:10.1016/j.ccm.2020.06.008

5. Rochwerg B, Brochard L, Elliott MW, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. 2017;50(2):1602426. doi:10.1183/13993003.02426-2016

6. Gong Y, Sankari A. Noninvasive Ventilation. Treasure Island (FL): StatPearls Publishing; 2022.

7. Hill NS, Brennan J, Garpestad E, Nava S. Nava, Stefano MD Noninvasive ventilation in acute respiratory failure. Crit Care Med. 2007;35(10):24022407. doi:10.1097/01.CCM.0000284587.36541.7F

8. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care setting: whereare we? Eur Respir J. 2008;31(4):874886. doi:10.1183/09031936.00143507

9. Karen E, et al. Non-invasive ventilation versus invasive weaning in critically ill adults: a systematic review and meta-analysis. Thorax. 2021;2021:216993. doi:10.1136/thoraxjnl-2021-216993

10. Frat J-P, Brugiere B, Ragot S, et al. Sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study. Respir Care. 2015;60(2):170178. doi:10.4187/respcare.03075

11. Mller W, Feng S, Domanski U, et al. Nasal high flow reduces dead space. J Appl Physiol. 2017;122(1):191197. doi:10.1152/japplphysiol.00584.2016

12. Cortegiani A, Longhini F, Madotto F, et al. High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial. Critical Care. 2020;24(1):692. doi:10.1186/s13054-020-03409-0

13. Xu Z, Zhu L, Zhan J, et al. The efficacy and safety of high-flow nasal cannula therapy in patients with COPD and type II respiratory failure: a meta-analysis and systematic review. Eur J Med Res. 2021;26(1):122. doi:10.1186/s40001-021-00587-7

14. Higgins JPT, Thomas J, Chandler J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. 2nd. Chichester (UK): John Wiley & Sons; 2019. http://www.cochrane-handbook.org. Accessed August 26, 2022.

15. Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:160. doi:10.1136/bmj.n160

16. Higgins JP, Altman DG, Gtzsche PC, et al.; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaborations tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928

17. Zhang JC, Wu FX, Meng LL, Zeng CY, Lu YQ. [A study on the effects and safety of sequential humidified high flow nasal cannula oxygenation therapy on the COPD patients after extubation].. Zhonghua Yi Xue Za Zhi. 2018;98(2):109112. doi:10.3760/cma.j.issn.0376-2491.2018.02.007

18. Yu ZH, Zhang R, Huang H, Li J, Geng S. Efficacy and safety of humidified high flow nasal cannula in chronic obstructive pulmonary disease complicated with type 2 respiratory failure patients after extubation: a randomized controlled trial. Acad j Second Military Med Univ. 2019;40(9):989994. doi:10.16781/j.0258-879x.2019.09.0989

19. Jing G, Li J, Hao D, et al. Comparison of high flow nasal cannula with noninvasive ventilation in chronic obstructive pulmonary disease patients with hypercapnia in preventing postextubation respiratory failure: a pilot randomized controlled trial. Res Nurs Health. 2019;42(3):217225. doi:10.1002/nur.21942

20. Yang SQ, Liu Z, Meng SQ, et al. [Application value of non-invasive ventilation combined with high flow nasal cannula oxygen therapy in sequential treatment of patients with chronic obstructive pulmonary disease after mechanical ventilation]. Zhonghua Yi Xue Za Zhi. 2020;100(27):21162120. Chinese. doi:10.3760/cma.j.cn112137-20200306-00616

21. Thille AW, Coudroy R, Nay MA, et al. Non-invasive ventilation alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation in COPD patients: a post hoc analysis of a randomized controlled trial. Ann Intensive Care. 2021;11(1):30. doi:10.1186/s13613-021-00823-7

22. Xu S, Liu X. Sequential treatment of chronic obstructive pulmonary disease concurrent with respiratory failure by high-flow nasal cannula therapy. Am J Transl Res. 2021;13(4):28312839.

23. Fang G, Wan Q, Tian Y, et al. [Comparative study on pros and cons of sequential high-flow nasal cannula and non-invasive positive pressure ventilation immediately following early extubated patients with severe respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021;33(10):12151220. Chinese. doi:10.3760/cma.j.cn121430-20210623-00939

24. Tan D, Walline JH, Ling B, et al. High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial. Crit Care. 2020;24(1):489doi:10.1186/s13054-020-03214-9.

25. Ouanes-Besbes L, Ouanes I, Dachraoui F, Dimassi S, Mebazaa A, Abroug F. Weaning difficult-to-wean chronic obstructive pulmonary disease patients: a pilot study comparing initial hemodynamic effects of levosimendan and dobutamine. J Crit Care. 2011;26(1):1521. doi:10.1016/j.jcrc.2010.01.002

26. Lindenauer PK, Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Hill NS. Outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease. JAMA Intern Med. 2014;174(12):19821993. doi:10.1001/jamainternmed.2014.5430

27. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173(2):164170. doi:10.1164/rccm.200505-718OC

28. Riera J, Prez P, Corts J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013;58(4):589596. doi:10.4187/respcare.02086

29. Chidekel A, Zhu Y, Wang J, Mosko JJ, Rodriguez E, Shaffer TH. The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells. Pulm Med. 2012;2012:380686. doi:10.1155/2012/380686

30. Chanques G, Constantin JM, Sauter M, et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35(6):9961003. doi:10.1007/s00134-009-1456-x

31. Hernndez G, Vaquero C, Gonzlez P, et al. Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: a Randomized Clinical Trial. JAMA. 2016;315(13):13541361. doi:10.1001/jama.2016.2711

32. Lee MK, Choi J, Park B, et al. High flow nasal cannulae oxygen therapy in acute-moderate hypercapnic respiratory failure. Clin Respir J. 2018;12(6):20462056. doi:10.1111/crj.12772

33. Roca O, Caralt B, Messika J, et al. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019;199(11):13681376. doi:10.1164/rccm.201803-0589OC

34. Karim HMR, Bharadwaj A, Mohammed Mujahid O. Relationship of ROX and Modified ROX index with High Flow Nasal Cannula Oxygen therapy in COVID-19 patients: an observational, pilot study. J Am Osteopath Assoc. 2022. doi:10.21203/rs.3.rs-1680854/v1

35. Karim HMR, Esquinas AM. Success or Failure of High-Flow Nasal Oxygen Therapy: the ROX Index Is Good, but a Modified ROX Index May Be Better. Am J Respir Crit Care Med. 2019;200(1):116117. doi:10.1164/rccm.201902-0419LE

36. Duan J, Han X, Bai L, et al. Assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients. Intensive Care Med. 2017;43(2):192199. doi:10.1007/s00134-016-4601-3

37. Longhini F, Pan C, Xie J, et al. New setting of neurally adjusted ventilatory assist for noninvasive ventilation by facial mask: a physiologic study. Crit Care. 2017;21(1):170. doi:10.1186/s13054-017-1761-7

38. Bruni A, Garofalo E, Pelaia C, et al. Patient-ventilator asynchrony in adult critically ill patients. Minerva Anestesiol. 2019;85(6):676688. doi:10.23736/S0375-9393.19.13436-0

39. Elshof J, Duiverman ML. Clinical evidence of nasal high-flow therapy in chronic obstructive pulmonary disease patients. Respiration. 2020;99(2):140153. doi:10.1159/000505583

40. Raza HA, Nokes B, Wesselius L, Long-Term Oxygen AN. Therapy in patients with chronic obstructive pulmonary disease and moderate hypoxemia. J Am Osteopath Assoc. 2018;118(10):663665. doi:10.7556/jaoa.2018.145

41. Jiang M, Song JJ, Guo XL, Tang YL, Li HB. Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation. Respir Care. 2015;60(12):17201728. doi:10.4187/respcare.03640

42. Rittayamai N, Phuangchoei P, Tscheikuna J, Praphruetkit N, Brochard L. Effects of high-flow nasal cannula and non-invasive ventilation on inspiratory effort in hypercapnic patients with chronic obstructive pulmonary disease: a preliminary study. Ann Intensive Care. 2019;9(1):122. doi:10.1186/s13613-019-0597-5

43. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(10):e121e141. doi:10.1164/rccm.202009-3608ST

44. Sang L, Nong L, Zheng Y, et al. Effect of high-flow nasal cannula versus conventional oxygen therapy and non-invasive ventilation for preventing reintubation: a Bayesian network meta-analysis and systematic review. J Thorac Dis. 2020;12(7):37253736. doi:10.21037/jtd-20-1050

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Therapeutic effect of HFNC and NIV in patients with AECOPD | COPD - Dove Medical Press

Five years ago today, the Food and Drug Administration issued a landmark approval for Kymriah, the first gene therapy available in the United States.

Cell and gene therapy products can transform how certain diseases are treated, offering life-extending and potentially curative benefits for patients living with life-threatening or debilitating diseases.

Propelled by significant research and development investments and scientific advances, the cell and gene therapy market has since experienced tremendous growth. Regulatory agencies around the world have approved a number of cell and gene therapy products including eight new therapies in the United States that target diseases with high unmet needs, ranging from cancer to retinal diseases.

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Based on a robust cell and gene therapy pipeline, experts forecast a wave of new approvals in the coming years, with the Alliance for Regenerative Medicine predicting 2022 could be record year for new gene therapies to treat rare diseases.

This trajectory holds substantial promise for patients worldwide. But right now the science is ahead of the U.S. health care system, leaving gaps that affect access the existence of a therapy is immaterial if patients cant access them.

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To realize the full potential of these therapies, its imperative to address existing challenges, such as payment and affordability-related barriers and reimbursement issues.

Reimbursement paying doctors and health care centers for the treatments they have administered is an important part of U.S. health care. Ensuring that cell and gene therapies are sufficiently reimbursed is essential for ensuring patient access.

Reimbursement isnt as simple as sending an invoice and receiving payment. Coverage (a payers decision to provide benefits for a specific product), coding (a unique identifier for a medicine) and payment levels (the amount an insurer will pay) affect how a product is reimbursed and each of those factors can vary based on the market, payer and therapy.

In the first few years after Kymriahs approval in the U.S., there wasnt a specific diagnosis-related group code for autologous cell therapies, a specific type of cell therapy in which a patients cells are collected, genetically modified, and then given back to the patient. The lack of a DRG code created uncertainty among providers about whether they would be appropriately reimbursed for the services they provided. The reimbursement landscape in the U.S. has since evolved: the Centers for Medicare & Medicaid Services issued and refined a diagnosis-related group code for autologous cell therapies, and a change in the status of the new technology add-on payment, which enables an additional payment to hospitals on top of the DRG payment amount.

These measures represent meaningful steps toward capturing the uniqueness of autologous cell therapies. But the frequent changes likely have contributed to confusion among health care providers about how to report the therapies and their charges.

Billing and coding errors resulted in significant differences in payment, and many hospitals were underpaid in 2019 and 2020, according to an analysis of Medicare payments by my colleagues on AmerisourceBergens consulting team. The disparities in payment underscore the importance of educating health care providers and their staff on the latest reimbursement changes and helping them master the dynamics of coding and billing, especially until a more permanent reimbursement solution is developed.

With more than 1,000 clinical trials now underway worldwide for cell and gene therapies, its increasingly important to establish solutions that address the current reimbursement challenges and establish more standardized pathways to cover the next wave of therapies and ensure they can reach the patients who need them. As regulators develop new guidance, biopharma companies should prioritize payer and stakeholder engagement earlier in the development life cycle to address questions related to payment and coverage decisions, such as:

Payers face this central question when evaluating cell and gene therapy products: How do we balance the potential long-term clinical value with the cost of the therapy and uncertainty regarding long-term durability at the time of regulatory approval? That challenge is compounded by the fact that many cell and gene therapies are one-time treatments, and patients can switch insurance carriers throughout their lifetimes, meaning the insurer that reimburses the cost of the treatment may not reap the benefits of saved health care costs down the road.

Historically, the vast majority of payers in the U.S. have used traditional techniques such as formulary or utilization management tools to manage the costs of cell and gene therapies. But payers have increasingly expressed interest in alternative payment models, such as reinsurance and outcomes-based agreements, in which payments are ultimately based on how well a treatment benefits patients. While outcomes-based agreements are particularly relevant for products with limited long-term clinical data and small patient populations, such as cell and gene therapies, certain factors including the Medicaid best price policy have prevented more widespread adoption of these agreements. A recently finalized rule by CMS aims to mitigate some of the potential challenges and concerns related to the Medicaid best price and foster more outcomes-based agreements between payers and biopharma companies for cell and gene therapies. That said, legal and compliance issues still pose barriers to these agreements.

Continued innovation in contracts and financial partnerships is essential to unlock access to cell and gene therapies. Biopharma companies and payers need to be flexible, agile, and open-minded in considering arrangements like outcomes-based agreements that better account for the long-term value and clinical outcomes over the term of the patients insurance policy. Considering the effort required to negotiate the value structure of outcomes-based agreements, I anticipate payers will be increasingly interested in participating in outcomes-based agreements for cell and gene therapies if there is a portfolio of products.

AmerisourceBergen, which I work for, provides pharmaceutical distribution services as well as solutions to help biopharma companies at every stage of the product lifecycle. The company is exploring ways to facilitate outcomes-based agreements that are objective, measurable, and easy to manage. We recently developed an outcomes-based agreement model for cell and gene therapies that aims to reduce financial exposure for biopharma companies, payers, and their client groups (namely employers with members who are eligible for these treatments) with the goal of improving patient access to cell and gene therapies.

The next five years hold tremendous promise for cell and gene therapies, including the potential to usher in allogenic cell therapies. Often referred to as off-the-shelf, allogenic cell therapies can be collected from a donor and then used to treat many patients rather than collecting and modifying each patients cells easing some of the manufacturing-related challenges associated with autologous cell therapies.

Meanwhile, the FDA continues to explore new initiatives to help accelerate the development of cell and gene therapy products. The director of the FDAs Center for Biologics Evaluation and Research, which regulates biological products for human use under applicable federal laws, recently shared his interest in establishing a gene therapy program in which sponsors would receive real-time feedback about their development programs from FDA reviewers. The program would help to inform the best approaches in developing gene therapies.

Based on the current pipeline of cell and gene therapy products, its possible that between 54 and 74 CGT products will be approved in the U.S. by 2030. Of course, even if these products receive approval and developers have the capacity to manufacture them at scale, the full potential of these therapies wont be realized unless the existing reimbursement and access barriers are addressed.

As the pipeline of cell and gene therapies continues to expand, its critical that the biopharma industry and the health care system create more standardized reimbursement pathways and introduce solutions that reduce barriers for the providers administering the therapies and the patients who need them.

Lung-I Cheng is the vice president of cell and gene therapy at AmerisourceBergen.

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Five years after Kymriah: Ensuring the next cell and gene therapies reach patients - STAT

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oi-Oneindia Staff

| Published: Tuesday, August 30, 2022, 18:08 [IST]

In present times we all are striving for better health. Healthcare professionals assist you in breathing, walking, eating, seeing, hearing, speaking, and moving correctly. They also help patients prevent illness, disease, and injury and lay down plans to fight and treat ailments of any kind.

From scientists, general physicians, neurologists, dentists, and therapists or alternative medicine practitioners, Indian doctors and other healthcare professionals have always been in the limelight for their significant achievements. Dressed in white coats, these warriors consistently make efforts toward saving lives and providing the best care to change the life of many.

Today we list the Top Healthcare professionals and leaders from different healthcare specializations who offer every patient the best clinical services based on their excellent diagnosis with medical or surgical interventions.

1. Dr. Niraj JhaDr. Niraj Jha is a well-known Neuro Physiotherapist and rehabilitation professional in the Mumbai region with global medical and social rehabilitation expertise. With over 16 years of experience in this field, Dr. Niraj Jha excels in neurorehabilitation, stroke rehabilitation, general community medicine, and other orthopaedic conditions using the latest evidence-based clinical practice. Dr. Jha has completed his Ph.D in Neurological Rehabilitation, Master of Physiotherapy in Neurology, and his Master's in Disability Rehabilitation at Tata Institute of Social Sciences, Mumbai. In addition, he has undergone and completed the Fellowship programme in Cardiac and Neurological Rehabilitation.

Presently he is serving as a District Chairperson - Medical Services of Lions Club of International. Physioworld is a Top 3 Best rated Physiotherapy Centre in Mumbai. He is also associated with premier organisations like UNICEF & WHO, as a Public health Consultant. Accredited with numerous honours, such as the best physiotherapist by the Sakal Idols of Maharashtra Award and the prestigious Front-Liners Unsung Heroes Red Carpet Award in 2022. He is considered among the best Neuro physiotherapist in India. Website - http://www.physioworld.org

2. Dr. Arvind GahlotDr. Arvind Gahlot is a name among the best Cardiothoracic Surgeons any country can have. He is a qualified M.Ch.(CVTS) and M.S(General Surgery) specialist and has outperformed 2000 successful open- heart surgeries. With over 15 years of experience, Dr. Arvind is the perfect 'Whisper to Roar' story in executing around 500 surgeries individually. He is associated with Mumbai's top hospitals like Saifee, Wockhardt, Raheja, Criticare, HN Reliance Foundation, SevenHills, AIMS, and Fortis Healthcare. He is the Most Prominent Cardiothoracic Surgeon of the Year - 2022, Mumbai. With achievements as an open-heart surgeon, he also vests his expertise in Minimally Invasive Heart Valve surgery, Bypass surgery, Vascular surgery, Valve replacement, and Repair. Dr. Arvind is an active participant in national and international conferences and his most cherished passion is being a lecturer for medical colleges. Website - http://www.drarvindgahlot.com

3. Dr. Aaditya PatakraoDr. Aaditya Patakrao, is renowned dentist from India, and known as A Celebrity Dentist.He is the owner of Dr. Aaditya's Advance Dental hospital, in Pune Maharashtra. He perform microscopic and laser root canals. Dr Aaditya has more than 10000 Root Canals surgeries and 2000 Dental Implants surgeries to his credit.

He has acquired Dental Implant course in Boston USA and Microscopic Laser skill from Germany. His Hospital is an International standardized and recognised by the European Medical Association. It has great ambience and It takes special care of the patients.Dr. Aaditya has a very skilled team to perform Dental treatments in a super advanced manner.

He has attended many international conferences to keep him upgraded in the field of dentistry.

Dr. Aaditya has been awarded many national and international awards for his quality work in Dentistry. Dr. Aaditya holds World Book of Records on his name for paying highest tax amongst all Dentist category. Recently he got Oscar of Dentistry Award. Website - http://www.aadityadentalcare.in

4. Dr Hetal Doshi, B.D.S (Mum), Post Graduate in Cosmetic Dentistry (USA), Associate Fellowship in Laser Dentistry (USA)Specialist in Cosmetic and Pediatric Dentistry.

Dr Hetal Doshi is one of the most dynamic Cosmetic Dental Surgeon and kids favourite dentist in Mumbai. With 19 years of experience Dr. Hetal is popularly known for her Painfree Dental treatments and specialises in providing Cosmetic, Laser & Implant dentistry to patients from infancy to adulthood.

Dr Hetal Doshi's Dental Care is one of the few clinics in Mumbai to provide Anxiety - Free Dentistry / Conscious Sedation commonly known as laughing gas using Nitrous oxide-oxygen sedation for a PAINFREE Dental experience for both children and adults .

Dr Hetal Doshi, director of Khandwala's Eye Hospital & Hem Polyclinic has been successful in Removing the Fear Out of Dentistry and creating 3000+ life changing smiles thereby instilling positive attitude towards dental treatments and changing the face of Dreadful, Painful Dentistry into a Painfree, Relaxed dental experience. Instagram ID - @dr.hetaldoshi

5. Dr Nikhil TariDr Nikhil Tari is the rising star in the Indian bodybuilding and fitness consultancy. Regarded as one of the most successful Indian bodybuilders, Dr Nikhil has been awarded as India's #1 bodybuilding & fitness consultant many times by various renowned institutions, including the "Health & Wellness Icon" - in Fitness & Bodybuilding by Midday. With a vast clinical experience of more than 15 years in this field and practising 24 years as a bodybuilder, he is a perfect blend of skills and experience. He successfully runs his Bodybuilding & Fitness clinic in Kandivali West Mumbai, Maharashtra. The expert professional is known for implementing different techniques for building muscle, and fitness programs, which helps curate specialized workouts and sports injury management with minimal lifestyle changes.

The pro fitness consultant actively shares deep insights on the subject related to bodybuilding fitness with thousands of his followers on multiple social media handles such as Youtube, Instagram, and Facebook.

His vision is to build an international-grade bodybuilding and fitness school in India and train world-class athletes who can win worldwide BODYBUILDING & FITNESS events. Website - http://www.drnikhiltari.business.site

6. Dr Bhasker Sharma -BHMS, MD, PhD (Homeo)Dr Bhasker Sharma is a highly-acclaimed homoeopathic doctor and physician in India and abroad. Dr Sharma hails from Siddharthnagar, Uttar Pradesh. The profound physician is on a mission to spread the world about homoeopathy and promote a healthy community through this form of holistic medicine. He continuously works hard to eradicate misconceptions related to homoeopathic treatment. He is a world-famous alternative medicine practitioner known for curing various diseases like renal stone, gastritis, leukoderma, piles, arthritis, skin diseases, diabetes, male sexual diseases, female sexual disease, ovarian cyst, PCOD, enlargement of the prostate gland, hair loss, weight loss, etc.

Dr Sharma has set over 30 dozen world records and has also been conferred with 58 dozen international and national honours in India and 12 dozen books published. He has over a dozen medical and literary works and publications to his credit. The Largest Homoeopathy Lesson is a significant feat accomplished at an event organised by Dr Sharma on August 21, 2018, in Rajkot, Gujarat. For achieving the feat, he was bestowed with the Guinness World Record. Website - http://www.drsharmafoundation.org

7. Dr Ameed Murad (Founder & MD of Vedaan)MBBS with Masters in Alternative Medicine & Applied Nutrition, Fellowship Functional Medicine, USA.A Modern Doctor powered by 450+ Years Of Heritage & Experience with Numerous national awards, scientific Patents and Disease Reversal specialist. Dr Ameed is loved & revered by millions of followers worldwide from bureaucrats, politicians, celebrities to the common man.Since 1565, The Murad family has been the bridge connecting India with the prestigious Tib-E-Unani (Greek-Arab system of medicinal science) way of Holistic natural healing through treatment of the root cause of illnesses, not just the symptoms but complete disease reversals.

Beginning his professional practice as a physician at the esteemed Apollo Hospital in New Delhi, Dr Ameed naturally developed a vision to integrate herbal remedies with modern medical science but also evolve it according to today's relevance.

With a team of doctors & scientists working alongside Dr Murad they have made discoveries in formulations & treatment methodologies. Numerous national and international pending patents in the nutraceutical arena add to the glamour. Website - http://www.Vedaan.com

8. Dr Anshuman Manaswi - MBBS, MS, DNB, M.Ch. - Senior consultant Plastic Surgery, MumbaiAnshuman Manaswi is a Senior Cosmetic and Plastic Surgeon based out of Mumbai, India with over 20 years of extensive surgical experience. He is the Founder and Director of one of the top centers for plastic surgery in India - La Transformation Plastic Surgery Centre. He is affiliated with best hospitals of Mumbai, the Nanavati Max Speciality Hospital & Bombay Hospital & Medical Research Centre.

He is quite popular with his incredible skill amonf the celebrities , but treats all his patients with equal passion He has trained many doctors in Cosmetology and Plastic Surgery.He has been accredited for many scientific research papers at international and national conferences and has scientific publications in journals of repute in his name. He is a recipient of Various Awards and accolades by reputed organisations. His name Appears in Marquis' Who's who World Bibliography as one of the top medical professionals in the world.He is one of the pioneers of Lymphedema Surgery in the country and takes pride in helping these unfortunate patients. Website - http://www.latransformatione.com

9. Dr Santosh ShettyDr Santosh Shetty is a renowned name in Orthopedics and Arthritis Care in Mumbai and has 20 plus years of experience. He is the Director Department of Joint Replacement in Surana Group of Hospitals and is amongst the top joint replacement surgeons to perform Robotic Joint Replacement Surgery in India. The doctor is a specialist in minimally invasive muscle sparing Robotic Cruciate Retaining Surgery (without cutting the muscles and the ligament ) using the Cuvis technology and is the first in the World to perform Robotic surgery of Both the Knee Joint in a single sitting using this Automatic technology and Opulent Gold CR Implants.

Dr Shetty has more than 10000 satisfied patients to his credit and has received numerous awards and accolades for his exemplary work in joint pain and arthritis and has also been recepient of the "Patient Satisfaction Award" and The Prestigious "Maharashtra Gaurav Award" for Exemplary Contribution in the field of Robotic Replacement.

Dr Shetty has pioneered Absolute PrecisionTM Technique for fast-track recovery and has been instrumental in bringing the latest cutting edge technology to offer the best to the patients suffering from arthritis. Website - http://www.drsantoshshetty.com

10. Dr. Surabhi DhanwalaDr. Surabhi Dhanwala is one of the celebrated Physiotherapists and Naturopathist in the country who is successfully running her Clinical Care and therapy centres in Pune (Maharashtra) and Dehradun (Uttarakhand). She has been in practice for over 18 years and has changed the lives of more than 19k patients. She is formally trained as BPT, MPT (Neuro), DNYS, CCH (1yr), and CHM (Thailand (1yr). In addition, the skilled doctor has received an Honorary Doctorate from South Western American University in Neuromuscular Rehabilitation and Acupressure.

The expert medical professional is known for her magical hands that can cure patients without surgeries by using treatments which are a fusion of modern science and ancient therapies. Dr Surabhi treats and heals people to heal through natural treatments and lifestyle changes.The ace doctor specialises in treating patients diagnosed with Knee or Hip Replacement, Frozen Shoulder, digestive track problems, diabetes and its associated ailments, Joint stiffness and dislocation, Retino Pigmentosa, Peripheral Neuro Pathy etc. Dr Surabhi has been bestowed with numerous awards. The most recent with the ET Change Makers Award 2022. Website - http://www.dhanwala.com

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Story first published: Tuesday, August 30, 2022, 18:08 [IST]

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Meet these renowned healthcare professionals who assist us in leading healthier lives - Oneindia