-
Scientific Reports Sep 2023Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis... (Meta-Analysis)
Meta-Analysis
Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis infection (LTBI) treatments, there is currently no evidence to support the notion that the benefits of these treatments outweigh the potential risks. This NMA aimed to conduct a comprehensive comparison and update of the efficacy, treatment completion rates and adverse events associated with recommended treatment options for LTBI for individuals with confirmed LTBI, as outlined in the 2020 World Health Organization (WHO) Consolidated Guidelines for TB preventive treatment. A comprehensive search of the MEDLINE and Scopus databases was conducted until April 2023. The NMA was applied to estimate the risk difference and corresponding 95% confidence interval (CI) using a combination of direct and indirect evidence. The risk-benefit assessment was employed to evaluate the feasibility of the extra benefits in relation to the extra risks. The primary outcomes of interest in this study were active TB disease, completion rates, and adverse events. The meta-analysis incorporated data from 15 studies, which collectively demonstrated that the administration of a placebo resulted in a significant increase in the risk of developing TB disease by 1.279%, compared to the daily intake of isoniazid for 6 months (6H). Furthermore, treatment completion rates were significantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin daily for 4 months (4R), as compared to 6H. Considering adverse events, the combination of 3HP, 4R, and isoniazid administered daily for 9 months (referred to as 9H) significantly decreased adverse events by 4.53% in comparison to 6H. The risk-benefit assessment showed that alternative treatment regimens (9H, 4R, 3HR and 3HP) had a lower incidence of adverse events, while demonstrating a higher efficacy in preventing TB, as compared to 6H. This review indicates that there were no significant differences observed among various active treatment options in terms of their efficacy in preventing active TB. Moreover, completion rates were higher in 3HP and 4R, and a reduction in adverse events was observed in 3HP, 4R, and 9H.
Topics: Humans; Antitubercular Agents; Isoniazid; Latent Tuberculosis; Network Meta-Analysis; Drug Therapy, Combination
PubMed: 37758777
DOI: 10.1038/s41598-023-43310-8 -
BMC Infectious Diseases Nov 2023Both tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and affect the absorption and metabolism for anti-TB drugs. Drug-resistant TB (DR-TB) with DM make control TB more difficult.
METHODS
This study was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. We searched PubMed, Excerpta Medica Database (EMBASE), Web of Science, ScienceDirect and Cochrance Library for literature published in English until July 2022. Papers were limited to those reporting the association between DM and treatment outcomes among DR-TB and multidrug-resistant TB (MDR-TB) patients. The strength of association was presented as odds ratios (ORs) and their 95% confidence intervals (CIs) using the fixed-effects or random-effects models. This study was registered with PROSPERO, number CRD: 42,022,350,214.
RESULTS
A total of twenty-five studies involving 16,905 DR-TB participants were included in the meta-analysis, of which 10,124 (59.89%) participants were MDR-TB patients, and 1,952 (11.54%) had DM history. In DR-TB patients, the pooled OR was 1.56 (95% CI: 1.24-1.96) for unsuccessful outcomes, 0.64 (95% CI: 0.44-0.94) for cured treatment outcomes, 0.63 (95% CI: 0.46-0.86) for completed treatment outcomes, and 1.28 (95% CI: 1.03-1.58) for treatment failure. Among MDR-TB patients, the pooled OR was 1.57 (95% CI: 1.20-2.04) for unsuccessful treatment outcomes, 0.55 (95% CI: 0.35-0.87) for cured treatment outcomes, 0.66 (95% CI: 0.46-0.93) for treatment completed treatment outcomes and 1.37 (95% CI: 1.08-1.75) for treatment failure.
CONCLUSION
DM is a risk factor for adverse outcomes of DR-TB or MDR-TB patients. Controlling hyperglycemia may contribute to the favorite prognosis of TB. Our findings support the importance for diagnosing DM in DR-TB /MDR-TB, and it is needed to control glucose and therapeutic monitoring during the treatment of DR-TB /MDR-TB patients.
Topics: Humans; Diabetes Mellitus; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Risk Factors; Treatment Outcome
PubMed: 37986146
DOI: 10.1186/s12879-023-08765-0 -
PloS One 2022Since multidrug-resistant tuberculosis (MDR-TB) is a significant public health problem worldwide, identifying associated risk factors is critical for developing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since multidrug-resistant tuberculosis (MDR-TB) is a significant public health problem worldwide, identifying associated risk factors is critical for developing appropriate control strategies.
METHODS
A systematic review and meta-analysis was conducted for identifying factors independently predicting MDR-TB. The random-effects model was used to determine pooled odds ratios (ORs) and respective 95% confidence intervals (CIs) for the related factors.
RESULTS
Of the 2301 retrieved reports, 28 studies were analyzed, assessing 3152 MDR-TB and 52715 DS-TB cases. Totally 22 related factors were analyzed. The pooled ORs were 1.478 (95%CI 1.077-2.028) for positive sputum AFB smear, 1.716 (95%CI 1.149-2.564) for lung cavity, 6.078 (95%CI 2.903-12.725) for previous TB disease and 5.427 (95%CI 3.469-8.490) for a history of anti-TB therapy. All Z test p values were below 0.05, indicating these parameters were significantly associated with MDR-TB.
CONCLUSIONS
Positive sputum AFB smear, lung cavity, previously diagnosed TB and a history of anti-TB therapy are significant risk factors for MDR-TB, which are independent of the clinical setting worldwide. Increased attention should be paid to cases with such parameters to achieve more effective TB control and avoid MDR-TB through the development of a global policy.
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Odds Ratio; Risk Factors; Sputum; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 35709161
DOI: 10.1371/journal.pone.0270003 -
PloS One 2020Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to synthesize the existing evidence on the relationship between depression and negative outcomes of TB treatment.
METHODS
We systematically reviewed studies that evaluated depressive symptoms (DS) directly or indirectly through psychological distress (PD) and measured negative treatment outcomes of drug-sensitive pulmonary TB, defined as death, loss to follow-up, or non-adherence. Sources included PubMed, Global Health Library, Embase, Scopus and Web of Science from inception to August 2019.
RESULTS
Of the 2,970 studies initially identified, eight articles were eligible for inclusion and two were used for the primary outcome meta-analysis. We found a strong association between DS and negative TB treatment outcomes (OR = 4.26; CI95%:2.33-7.79; I2 = 0%). DS were also associated with loss to follow-up (OR = 8.70; CI95%:6.50-11.64; I2 = 0%) and death (OR = 2.85; CI95%:1.52-5.36; I2 = 0%). Non-adherence was not associated with DS and PD (OR = 1.34; CI95%:0.70-2.72; I2 = 94.36) or PD alone (OR = 0.92; CI95%:0.81-1.05; I2 = 0%).
CONCLUSIONS
DS are associated with the negative TB treatment outcomes of death and loss to follow-up. Considerable heterogeneity exists in the definition of depression and outcomes such as non-adherence across the limited number of studies on this topic.
Topics: Antitubercular Agents; Databases, Factual; Depression; Humans; Odds Ratio; Tuberculosis
PubMed: 31923280
DOI: 10.1371/journal.pone.0227472 -
Frontiers in Immunology 2022This study aimed to compare the efficacy and safety (infection events) between rituximab (RTX), tacrolimus (TAC), mycophenolate mofetil (MMF), and cyclophosphamide (CYC)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to compare the efficacy and safety (infection events) between rituximab (RTX), tacrolimus (TAC), mycophenolate mofetil (MMF), and cyclophosphamide (CYC) as induction therapies in lupus nephritis (LN).
METHODS
Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched from inception up to December 9, 2021. Bayesian network meta-analysis was used to combine the direct and indirect evidence of different drugs for LN patients. The pooled relative effects were shown using odds ratios (ORs) and 95% credible intervals (CrIs).
RESULTS
Nineteen studies (1,566 patients) met the inclusion criteria and were selected in the present study. The network meta-analysis reported that no statistically significant differences were found in partial remission (PR) and infection among the four drugs. RTX showed a significantly higher complete remission (CR) than MMF (OR = 2.60, 95% CrI = 1.00-7.10) and seemed to be more effective than CYC (OR = 4.20, 95% CrI = 1.70-14.00). MMF had a better CR than CYC (OR = 1.60, 95% CrI = 1.00-3.20). TAC presented a better overall response than CYC (OR = 3.70, 95% CrI = 1.20-12.00). Regarding CR and overall response, the maximum surface under the cumulative ranking curve (SUCRA) values were 96.94% for RTX and 80.15% for TAC. The maximum SUCRA value of infection reaction was 74.98% for RTX and the minimum value was 30.17% for TAC, respectively.
CONCLUSIONS
RTX and TAC were the most effective drugs for induction remission in LN. Among the four drugs, TAC had the lowest probability of infection, and RTX showed the highest probability of experiencing an infection. This meta-analysis could not conclude about other adverse events.
Topics: Bayes Theorem; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Mycophenolic Acid; Network Meta-Analysis; Rituximab; Tacrolimus; Treatment Outcome
PubMed: 35444666
DOI: 10.3389/fimmu.2022.859380 -
Transplant Infectious Disease : An... Dec 2022We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.
METHODS
We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.
RESULTS
Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).
INTERPRETATION
Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.
Topics: Humans; Abatacept; COVID-19; COVID-19 Vaccines; Mycophenolic Acid; Organ Transplantation; Transplant Recipients
PubMed: 35924679
DOI: 10.1111/tid.13926 -
Medicine Sep 2020Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN.
METHODS
Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions.
RESULTS
Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III-V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230-0.719)] and complete remission [RR = 1.231, 95%CI (1.055-1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081-0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014-0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (-0.060-0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532-0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564-0.724)], independent of race.
CONCLUSIONS
MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III-V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.
Topics: Adult; Cyclophosphamide; Female; Humans; Lupus Nephritis; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 32957400
DOI: 10.1097/MD.0000000000022328 -
Antimicrobial Resistance and Infection... Mar 2023Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet its extent is not well evaluated, especially in low-middle income countries. It is... (Review)
Review
BACKGROUND
Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet its extent is not well evaluated, especially in low-middle income countries. It is challenging to promote policies without focusing on healthcare systems at a local level, therefore a baseline assessment of the AMR occurrence is a priority. This study aimed to look at published papers relating to the availability of AMR data in Zambia as a means of establishing an overview of the situation, to help inform future decisions.
METHODS
PubMed, Cochrane Libraries, Medical Journal of Zambia and African Journals Online databases were searched from inception to April 2021 for articles published in English in accordance with the PRISMA guidelines. Retrieval and screening of article was done using a structured search protocol with strict inclusion/exclusion criteria.
RESULTS
A total of 716 articles were retrieved, of which 25 articles met inclusion criteria for final analysis. AMR data was not available for six of the ten provinces of Zambia. Twenty-one different isolates from the human health, animal health and environmental health sectors were tested against 36 antimicrobial agents, across 13 classes of antibiotics. All the studies showed a degree of resistance to more than one class of antimicrobials. Majority of the studies focused on antibiotics, with only three studies (12%) highlighting antiretroviral resistance. Antitubercular drugs were addressed in only five studies (20%). No studies focused on antifungals. The most common organisms tested, across all three sectors, were Staphylococcus aureus, with a diverse range of resistance patterns found; followed by Escherichia coli with a high resistance rate found to cephalosporins (24-100%) and fluoroquinolones (20-100%).
CONCLUSIONS
This review highlights three important findings. Firstly, AMR is understudied in Zambia. Secondly, the level of resistance to commonly prescribed antibiotics is significant across the human, animal, and environmental sectors. Thirdly, this review suggests that improved standardization of antimicrobial susceptibility testing in Zambia could help to better delineate AMR patterns, allow comparisons across different locations and tracking of AMR evolution over time.
Topics: Animals; Humans; Zambia; Drug Resistance, Bacterial; One Health; Antitubercular Agents; Anti-Retroviral Agents; Escherichia coli
PubMed: 36869351
DOI: 10.1186/s13756-023-01224-0 -
The Cochrane Database of Systematic... Dec 2022Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms... (Review)
Review
BACKGROUND
Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers. Meticillin-resistant Staphylococcus aureus (MRSA) has emerged not only as an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer on people with cystic fibrosis a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.
OBJECTIVES
To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including Pseudomonas aeruginosa), increased adverse effects from drugs, or both.
SEARCH METHODS
We identified randomised and quasi-randomised controlled trials by searching the Cochrane Cystic Fibrosis and Genetic Disorders (CFGD) Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE and three clinical trials registries; by handsearching article reference lists; and through contact with experts in the field. We last searched the CFGD Group's Cystic Fibrosis Trials Register on 4 October 2021, and the ongoing trials registries on 31 January 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs of any combinations of topical, inhaled, oral or intravenous antimicrobials primarily aimed at eradicating MRSA compared with placebo, standard treatment or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and used the GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
The review includes three RCTs with 135 participants with MRSA infection. Two trials compared active treatment versus observation only and one trial compared active treatment with placebo. Active treatment versus observation In both trials (106 participants), active treatment consisted of oral trimethoprim and sulfamethoxazole combined with rifampicin. One trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. Both trials reported successful eradication of MRSA in people with cystic fibrosis, but they used different definitions of eradication. One trial (45 participants) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures compared to control (odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence). However, by day 168 of follow-up, there was no difference between groups in the proportion of participants who remained MRSA-negative (OR 1.17, 95% CI 0.31 to 4.42; low-certainty evidence). The second trial defined successful eradication as the absence of MRSA following treatment in at least three cultures over a period of six months. We are uncertain if the intervention led to results favouring the treatment group as the certainty of the evidence was very low (OR 2.74, 95% CI 0.64 to 11.75). There were no differences between groups in the remaining outcomes for this comparison: quality of life, frequency of exacerbations or adverse effects (all low-certainty evidence) or the change from baseline in lung function or weight (both very low-certainty evidence). The time until next positive MRSA isolate was not reported. The included trials found no differences between groups in terms of nasal colonisation with MRSA. While not a specific outcome of this review, investigators from one study reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control (rate ratio 0.22, 95% CI 0.05 to 0.72; P = 0.01). Nebulised vancomycin with oral antibiotics versus nebulised placebo with oral antibiotics The third trial (29 participants) defined eradication as a negative respiratory sample for MRSA at one month following completion of treatment. No differences were reported in MRSA eradication between treatment arms (OR 1.00, 95% CI 0.14 to 7.39; low-certainty evidence). No differences between groups were seen in lung function or adverse effects (low-certainty evidence), in quality of life (very low-certainty evidence) or nasal colonisation with MRSA. The trial did not report on the change in weight or frequency of exacerbations. AUTHORS' CONCLUSIONS: Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, follow-up at three or six months showed no difference between treatment and control in the proportion of participants remaining MRSA-negative. Moreover, the longer-term clinical consequences - in terms of lung function, mortality and cost of care - remain unclear. Using GRADE methodology, we judged the certainty of the evidence provided by this review to be very low to low, due to potential biases from the open-label design, high rates of attrition and small sample sizes. Based on the available evidence, we believe that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Cystic Fibrosis; Pseudomonas aeruginosa; Anti-Bacterial Agents; Rifampin
PubMed: 36511181
DOI: 10.1002/14651858.CD009650.pub5 -
European Journal of Drug Metabolism and... Nov 2021One approach of therapeutic drug monitoring in the case of mycophenolic acid (MPA) is a limited sampling strategy (LSS), which allows the evaluation of the area under...
BACKGROUND AND OBJECTIVE
One approach of therapeutic drug monitoring in the case of mycophenolic acid (MPA) is a limited sampling strategy (LSS), which allows the evaluation of the area under the concentration-time curve (AUC) based on few concentrations. The aim of this systematic review was to review the MPA LSSs and define the most frequent time points for MPA determination in patients with different indications for mycophenolate mofetil (MMF) administration.
METHODS
The literature was comprehensively searched in July 2021 using PubMed, Scopus, and Medline databases. Original articles determining multiple linear regression (MLR)-based LSSs for MPA and its free form (fMPA) were included. Studies on enteric-coated mycophenolic sodium, previously established LSS, Bayesian estimator, and different than twice a day dosing were excluded. Data were analyzed separately for (1) adult renal transplant recipients, (2) adults with other than renal transplantation indication, and (3) for pediatric patients.
RESULTS
A total of 27, 17, and 11 studies were found for groups 1, 2, and 3, respectively, and 126 MLR-based LSS formulae (n = 120 for MPA, n = 6 for fMPA) were included in the review. Three time-point equations were the most frequent. Four MPA LSSs: 2.8401 + 5.7435 × C0 + 0.2655 × C0.5 + 1.1546 × C1 + 2.8971 × C4 for adult renal transplant recipients, 1.783 + 1.248 × C1 + 0.888 × C2 + 8.027 × C4 for adults after islet transplantation, 0.10 + 11.15 × C0 + 0.42 × C1 + 2.80 × C2 for adults after heart transplantation, and 8.217 + 3.163 × C0 + 0.994 × C1 + 1.334 × C2 + 4.183 × C4 for pediatric renal transplant recipients, plus one fMPA LSS, 34.2 + 1.12 × C1 + 1.29 × C2 + 2.28 × C4 + 3.95 × C6 for adult liver transplant recipients, seemed to be the most promising and should be validated in independent patient groups before introduction into clinical practice. The LSSs for pediatric patients were few and not fully characterized. There were only a few fMPA LSSs although fMPA is a pharmacologically active form of the drug.
CONCLUSIONS
The review includes updated MPA LSSs, e.g., for different MPA formulations (suspension, dispersible tablets), generic form, and intravenous administration for adult and pediatric patients, and emphasizes the need of individual therapeutic approaches according to MMF indication. Five MLR-based MPA LSSs might be implemented into clinical practice after evaluation in independent groups of patients. Further studies are required, e.g., to establish fMPA LSS in pediatric patients.
Topics: Area Under Curve; Bayes Theorem; Humans; Linear Models; Mycophenolic Acid
PubMed: 34480746
DOI: 10.1007/s13318-021-00713-0