-
The Cochrane Database of Systematic... Jun 2023Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development... (Review)
Review
Granulocyte colony-stimulating factor with or without stem or progenitor cell or growth factors infusion for people with compensated or decompensated advanced chronic liver disease.
BACKGROUND
Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development of complications of portal hypertension and liver dysfunction. Advanced chronic liver disease is considered responsible for more than one million deaths annually worldwide. No treatment is available to specifically target fibrosis and cirrhosis; liver transplantation remains the only curative option. Researchers are investigating strategies to restore liver functionality to avoid or slow progression towards end-stage liver disease. Cytokine mobilisation of stem cells from the bone marrow to the liver could improve liver function. Granulocyte colony-stimulating factor (G-CSF) is a 175-amino-acid protein currently available for mobilisation of haematopoietic stem cells from the bone marrow. Multiple courses of G-CSF, with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, might be associated with accelerated hepatic regeneration, improved liver function, and survival.
OBJECTIVES
To evaluate the benefits and harms of G-CSF with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, compared with no intervention or placebo in people with compensated or decompensated advanced chronic liver disease.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trial registers (October 2022) together with reference-checking and web-searching to identify additional studies. We applied no restrictions on language and document type.
SELECTION CRITERIA
We only included randomised clinical trials comparing G-CSF, independent of the schedule of administration, as a single treatment or combined with stem or progenitor cell infusion, or with other medical co-interventions, with no intervention or placebo, in adults with chronic compensated or decompensated advanced chronic liver disease or acute-on-chronic liver failure. We included trials irrespective of publication type, publication status, outcomes reported, or language.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane procedures. All-cause mortality, serious adverse events, and health-related quality of life were our primary outcomes, and liver disease-related morbidity, non-serious adverse events, and no improvement of liver function scores were our secondary outcomes. We undertook meta-analyses, based on intention-to-treat, and presented results using risk ratios (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) and I statistic values as a marker of heterogeneity. We assessed all outcomes at maximum follow-up. We determined the certainty of evidence using GRADE, evaluated the risk of small-study effects in regression analyses, and conducted subgroup and sensitivity analyses.
MAIN RESULTS
We included 20 trials (1419 participants; sample size ranged from 28 to 259), which lasted between 11 and 57 months. Nineteen trials included only participants with decompensated cirrhosis; in one trial, 30% had compensated cirrhosis. The included trials were conducted in Asia (15), Europe (four), and the USA (one). Not all trials provided data for our outcomes. All trials reported data allowing intention-to-treat analyses. The experimental intervention consisted of G-CSF alone or G-CSF plus any of the following: growth hormone, erythropoietin, N-acetyl cysteine, infusion of CD133-positive haemopoietic stem cells, or infusion of autologous bone marrow mononuclear cells. The control group consisted of no intervention in 15 trials and placebo (normal saline) in five trials. Standard medical therapy (antivirals, alcohol abstinence, nutrition, diuretics, β-blockers, selective intestinal decontamination, pentoxifylline, prednisolone, and other supportive measures depending on the clinical status and requirement) was administered equally to the trial groups. Very low-certainty evidence suggested a decrease in mortality with G-CSF, administered alone or in combination with any of the above, versus placebo (RR 0.53, 95% CI 0.38 to 0.72; I = 75%; 1419 participants; 20 trials). Very low-certainty evidence suggested no difference in serious adverse events (G-CSF alone or in combination versus placebo: RR 1.03, 95% CI 0.66 to 1.61; I = 66%; 315 participants; three trials). Eight trials, with 518 participants, reported no serious adverse events. Two trials, with 165 participants, used two components of the quality of life score for assessment, with ranges from 0 to 100, where higher scores indicate better quality of life, with a mean increase from baseline of the physical component summary of 20.7 (95% CI 17.4 to 24.0; very low-certainty evidence) and a mean increase from baseline of the mental component summary of 27.8 (95% CI 12.3 to 43.3; very low-certainty evidence). G-CSF, alone or in combination, suggested a beneficial effect on the proportion of participants who developed one or more liver disease-related complications (RR 0.40, 95% CI 0.17 to 0.92; I = 62%; 195 participants; four trials; very low-certainty evidence). When we analysed the occurrences of single complications, there was no suggestion of a difference between G-CSF, alone or in combination, versus control, in participants in need of liver transplantation (RR 0.85, 95% CI 0.39 to 1.85; 692 participants; five trials), in the development of hepatorenal syndrome (RR 0.65, 95% CI 0.33 to 1.30; 520 participants; six trials), in the occurrence of variceal bleeding (RR 0.68, 95% CI 0.37 to 1.23; 614 participants; eight trials), and in the development of encephalopathy (RR 0.56, 95% CI 0.31 to 1.01; 605 participants; seven trials) (very low-certainty evidence). The same comparison suggested that G-CSF reduces the development of infections (including sepsis) (RR 0.50, 95% CI 0.29 to 0.84; 583 participants; eight trials) and does not improve liver function scores (RR 0.67, 95% CI 0.53 to 0.86; 319 participants; two trials) (very low-certainty evidence).
AUTHORS' CONCLUSIONS
G-CSF, alone or in combination, seems to decrease mortality in people with decompensated advanced chronic liver disease of whatever aetiology and with or without acute-on-chronic liver failure, but the certainty of evidence is very low because of high risk of bias, inconsistency, and imprecision. The results of trials conducted in Asia and Europe were discrepant; this could not be explained by differences in participant selection, intervention, and outcome measurement. Data on serious adverse events and health-related quality of life were few and inconsistently reported. The evidence is also very uncertain regarding the occurrence of one or more liver disease-related complications. We lack high-quality, global randomised clinical trials assessing the effect of G-CSF on clinically relevant outcomes.
Topics: Adult; Humans; Esophageal and Gastric Varices; Quality of Life; Acute-On-Chronic Liver Failure; Gastrointestinal Hemorrhage; Liver Cirrhosis; Stem Cells; Granulocyte Colony-Stimulating Factor; Intercellular Signaling Peptides and Proteins; Erythropoietin; Growth Hormone
PubMed: 37278488
DOI: 10.1002/14651858.CD013532.pub2 -
BMJ Open Apr 2021To summarise current evidence on the use of pentoxifylline (PTX) to prevent contrast-induced nephropathy (CIN). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To summarise current evidence on the use of pentoxifylline (PTX) to prevent contrast-induced nephropathy (CIN).
METHODS
The PubMed, Embase and CENTRAL databases were searched for randomised controlled trials including patients with and without PTX undergoing contrast media exposure. We analysed the incidence of CIN and serum creatinine changes before and after contrast media exposure. All statistical analyses were conducted with Review Manager V.5.3.
RESULTS
We finally enrolled in seven randomised controlled trials with a total of 1484 patients in this analysis. All of seven included studies were performed in patients undergoing angioplasty or stenting. The overall rates of CIN were 8.8% and 10.4% in the PTX groups and control groups, respectively. However, no significant reduction in the CIN rate was observed in the patients treated with PTX compared with the control groups (OR 0.81, 95% CI 0.57 to 1.13, I=0, p=0.21). All studies reported no hospital mortality and the new requirement for dialysis during the trials.
CONCLUSION
Perioperative administration of PTX to patients undergoing angioplasty did not significantly reduce the development of CIN but showed some weak tendency of lower serum creatinine increase. Based on the available trials, the evidence does not support the administration of PTX for the prevention of CIN. More trials with larger sample sizes are needed to evaluate the role of PTX in CIN prevention.
Topics: Contrast Media; Coronary Angiography; Creatinine; Humans; Kidney Diseases; Pentoxifylline; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 33945499
DOI: 10.1136/bmjopen-2020-043436 -
Brain, Behavior, & Immunity - Health Feb 2023A growing amount of research suggests that inflammatory responses have a crucial role in the complex pathophysiology of Major Depressive Disorder (MDD), a disabling... (Review)
Review
A growing amount of research suggests that inflammatory responses have a crucial role in the complex pathophysiology of Major Depressive Disorder (MDD), a disabling medical condition. The present review has two primary goals. Firstly, to highlight and summarize results from studies that investigated the changes of IL-6 in MDD patients before and after combined treatment. The second aim is to enlighten the need for further research on the difference in the concentration of the pro-inflammatory cytokines between MDD and Treatment-Resistant MDD. The protocol of this study was written using PRISMA, and it is registered at PROSPERO (identification: CRD42021289233). We searched the following bibliographic databases to identify potentially eligible articles without any time limit until September 2021: Pubmed, Web of Science, Scopus, PsycINFO. As they met the eligibility criteria, 14 articles were included in this systematic review. The selected studies assessed twelve different elements as an adjunction to the standard pharmacotherapy (ECT, Ketamine, CBT, NCT, Ketoprofene, Lithium, Celecoxib, Metformin tDCS, Pentoxifylline, ethyl-EPA, Zinc). Significant results were found in the studies that analyzed the impact of combined treatment with the adjunction of the following elements: ECT, Ketamine, CBT, NCT, Celecoxib, Metformin, and Pentoxifylline. Overall, this systematic review identifies several potentially beneficial combined treatments for MDD patients. Further evidence is needed to confirm the efficacy of reducing IL-6 levels in patients with Treatment-Resistant MDD.
PubMed: 36624849
DOI: 10.1016/j.bbih.2022.100579 -
Frontiers in Medicine 2021Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in...
Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.
PubMed: 34631742
DOI: 10.3389/fmed.2021.718896 -
Advances in Radiation Oncology 2022Radiation therapy can affect normal tissues in patients with breast cancer, causing adverse effects such as fibrosis. Although there are several interventions for...
PURPOSE
Radiation therapy can affect normal tissues in patients with breast cancer, causing adverse effects such as fibrosis. Although there are several interventions for radiation-induced fibrosis, the efficacy of these procedures is still unclear. The purpose of this review is to evaluate the efficacy of interventions for radiation-induced fibrosis in patients with breast cancer.
METHODS AND MATERIALS
This is a systematic review of randomized clinical trials. Studies that compared any intervention for fibrosis to another intervention, placebo, or no intervention were included. Outcomes assessed were fibrosis, adverse events, quality of life, treatment adherence, pain, and functionality.
RESULTS
A total of 2501 publications were found, and 7 studies were selected because they met the inclusion criteria. The interventions for fibrosis were pentoxifylline and vitamin E, grape seed extract, kinesiotherapy, and endermotherapy. The results showed great heterogeneity in the treatment protocols for radiation-induced fibrosis in patients with breast cancer and in their evaluation metrics. The meta-analyses showed no benefit in using pentoxifylline and vitamin E compared with placebo or no intervention (standardized mean difference: -0.30; 95% confidence interval, -0.79 to 0.20; = .24 [very low evidence]) compared with placebo and vitamin E (standardized mean difference: -0.09; 95% confidence interval, -0.66 to 0.49; = .77 [moderate evidence]), respectively, assessed by the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, and Analytic (LENT-SOMA) scoring scale.
CONCLUSIONS
The effectiveness of these interventions for the treatment of radiation-induced fibrosis in patients with breast cancer could not be determined. Although isolated studies show significant results favorable to the experimental groups, caution should be exercised in these findings because of the small number, small sample size, and high risk of bias presented by some of the included studies, which makes the recommendation for clinical practice still weak.
PubMed: 35647406
DOI: 10.1016/j.adro.2022.100912 -
Dermatology Reports Nov 2022Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). Although rare, the condition may progress...
Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). Although rare, the condition may progress to involve serious complications and even lead to fatal outcomes if diagnosis and appropriate treatment is delayed. A PubMed search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines was performed to find cases of FUMHD from the earliest records to October 2021. Treatments, complications, and patient outcomes were extracted from the literature and summarized, while a review of quality was also performed. A total of 63 publications with 68 patients were found. Successful treatment modalities for FUMHD included antibiotics, antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide, Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline, and ultraviolet B phototherapy. Out of 68 patients, 55 patients had their condition fully resolved and 13 cases were fatal. Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis, but mucosal involvement did not affect mortality risk. Overall, the publications had low risk of bias, but most lacked adequate follow-up periods. FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly defined diagnostic criteria and optimum treatment. Further studies with larger patient populations and longer follow-up periods may lead to refinement of diagnostic criteria, establish an optimum treatment regimen, and better estimate the likelihood of recurrence.
PubMed: 36483219
DOI: 10.4081/dr.2022.9492 -
Journal of Personalized Medicine Sep 2023Acute ischemia of the glands is a severe complication after circumcision. We outline the challenging case of a seventeen-year-old boy with glandular ischemia (GI) that... (Review)
Review
Acute ischemia of the glands is a severe complication after circumcision. We outline the challenging case of a seventeen-year-old boy with glandular ischemia (GI) that appeared shortly after circumcision. Methods: We present a case report and literature review related to glans ischemia, and the complications of circumcision are reviewed. We note that there are very few cases described in the literature. Our patient was successfully treated with hyperbaric oxygen therapy (HBOT) after four days of no positive effect after all medical and surgical treatments written in the literature: Subcutaneous enoxaparin, local application of a glyceryl trinitrate, continuous epidural perfusion, intravenous pentoxifylline, alprostadil, intraoperative drainage, and aspiration with saline solution and epinephrine. Clinical improvement was noted at the first session of HBOT. A number of days after the operation, the penis looked normal and was healing. Complete healing of the penile glans was successfully realized one month after surgery. Conclusion: Based on the review and the case presented, we conclude that HBOT is the treatment of choice for acute ischemia of the penile glans, especially when other treatments do not work.
PubMed: 37763138
DOI: 10.3390/jpm13091370 -
Italian Journal of Pediatrics Aug 2019Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of pentoxifylline treatment for neonatal sepsis.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of pentoxifylline treatment on neonatal sepsis are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model.
RESULTS
Seven RCTs involving 439 patients are included in the meta-analysis. Compared with control intervention for neonatal sepsis, pentoxifylline treatment is associated with reduced hospital stay (Std. MD = -0.61; 95% CI = -0.93 to - 0.29; P = 0.0002) and metabolic acidosis (RR = 0.38; 95% CI = 0.22 to 0.66; P = 0.0006), but has no remarkable impact on mortality (RR = 0.59; 95% CI = 0.30 to 1.16; P = 0.13), serum TNF-α (Std. MD = -0.38; 95% CI = -1.29 to 0.52; P = 0.41), serum CRP (Std. MD = -0.25; 95% CI = -0.92 to 0.42; P = 0.47), plasma IL-6 (Std. MD = -0.13; 95% CI = -0.41 to 0.15; P = 0.37), disseminated intravascular coagulopathy (RR = 0.55; 95% CI = 0.25 to 1.21; P = 0.14), and oliguria/anuria (RR = 0.77; 95% CI = 0.28 to 2.16; P = 0.62). In addition, pentoxifylline treatment can significantly reduce mortality (RR = 0.50; 95% CI = 0.29 to 0.88; P = 0.02) after excluding the study conducted by Akdag during the sensivity analysis.
CONCLUSIONS
Pentoxifylline treatment may be associated with reduced mortality and hospital stay in neonatal sepsis.
Topics: Humans; Infant; Infant, Newborn; Neonatal Sepsis; Pentoxifylline; Phosphodiesterase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 31439016
DOI: 10.1186/s13052-019-0697-8 -
The Cochrane Database of Systematic... Aug 2020On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.
OBJECTIVES
To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).
SEARCH METHODS
We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic
PubMed: 32853410
DOI: 10.1002/14651858.CD004834.pub3 -
Respiratory Research Aug 2020The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes.
METHODS
This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events.
RESULTS
Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments.
CONCLUSIONS
Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Tuberculosis, Pulmonary; Vitamin D
PubMed: 32847532
DOI: 10.1186/s12931-020-01488-9