Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. OBJECTIVES: To evaluate the efficacy and safety of ERT for AFD. MATERIALS AND METHODS: For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. RESULTS: 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. CONCLUSIONS: Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials.

The aim of this study as to analyze published evidence regarding the effectiveness of aromatase inhibitor therapy on improving spermatogenesis in infertile men. We carried out a systematic review of randomized controlled trials. The date of the most recent search was October 4, 2015. Two authors independently selected relevant clinical trials, assessing their methodological quality and extracting data. Three studies were included in this review with a total of 100 participants; however, we were able to include data from only 54 participants in the analysis. In the representation of meta-analysis with a single study comparing testolactone versus placebo, related to the hormone concentrations, there was a statistically significance difference favoring the use of testolactone for Luteinizing Hormone (LH); Estrogen (E2); free Testosterone (free T); free Estrogen (free E2); 17-Hydroxyprogesterone (17OHP); prolactin (PRL). In another analysis from a single study comparing letrozole versus anastrozole, there was also a statistically significance difference favoring the use of letrozole for the increase in both the sperm count and LH. There is only low quality evidence regarding the effectiveness of aromatase inhibitor therapy in infertile men. Further trials are needed with standardized interventions and outcomes.

Differences between the real and the desired worlds in the results of clinical trials.

OBJECTIVE: We refer to the effectiveness (known as pragmatic or real world) and efficacy (known as explanatory or desired or ideal world) of interventions. However, these terms seem to be randomly chosen by investigators who design clinical trials and do not always reflect the true purpose of the study. A pragmatic-explanatory continuum indicator summary tool was thus developed with the aim of identifying the characteristics of clinical trials that distinguish between effectiveness and efficacy issues. We verified whether clinical trials used the criteria proposed by the indicator summary tool, and we categorized these clinical trials according to a new classification. METHOD: A systematic survey of randomized clinical trials was performed. We added a score ranging from 0 (more efficacious) to 10 (more effective) to each domain of the indicator summary tool and proposed the following classifications: high efficacy (<25), moderate efficacy (25-50), moderate effectiveness (51-75), and high effectiveness (<75). RESULTS: A total of 844 randomized trials were analyzed. No analyzed trials used the criteria proposed by the indicator summary tool. Approximately 44% of the trials were classified as having moderate effectiveness, and 43.82% were classified as having moderate efficacy. CONCLUSIONS: Most clinical trials used the term "efficacy" to illustrate the application of results in clinical practice, but the majority of those were classified as having moderate effectiveness according to our proposed score. The classification based on the 0-100 score is still highly subjective and can be easily misunderstood in all domains based on each investigator's own experiences and knowledge.

Differences between the real and the desired worlds in the results of clinical trials

OBJECTIVE:We refer to the effectiveness (known as pragmatic or real world) and efficacy (known as explanatory or desired or ideal world) of interventions. However, these terms seem to be randomly chosen by investigators who design clinical trials and do not always reflect the true purpose of the study. A pragmatic-explanatory continuum indicator summary tool was thus developed with the aim of identifying the characteristics of clinical trials that distinguish between effectiveness and efficacy issues. We verified whether clinical trials used the criteria proposed by the indicator summary tool, and we categorized these clinical trials according to a new classification.METHOD:A systematic survey of randomized clinical trials was performed. We added a score ranging from 0 (more efficacious) to 10 (more effective) to each domain of the indicator summary tool and proposed the following classifications: high efficacy (<25), moderate efficacy (25-50), moderate effectiveness (51-75), and high effectiveness (<75).RESULTS:A total of 844 randomized trials were analyzed. No analyzed trials used the criteria proposed by the indicator summary tool. Approximately 44% of the trials were classified as having moderate effectiveness, and 43.82% were classified as having moderate efficacy.CONCLUSIONS:Most clinical trials used the term “efficacy” to illustrate the application of results in clinical practice, but the majority of those were classified as having moderate effectiveness according to our proposed score. The classification based on the 0-100 score is still highly subjective and can be easily misunderstood in all domains based on each investigator’s own experiences and knowledge.

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies.

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention's effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient's wishes and circumstances in the absence of high-quality primary studies. It's not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention´s effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient´s wishes and circumstances in the absence of high-quality primary studies. It´s not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.(AU)

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention´s effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient´s wishes and circumstances in the absence of high-quality primary studies. It´s not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.

Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies.

UNLABELLED: Study Type - Therapy (systematic review). Level of Evidence 2b What's known on the subject? and What does the study add? The oncological success of partial nephrectomy in the treatment of small renal masses is well established. However, partial nephrectomy has largely supplanted the radical approach. In the last decade, laparoscopy has been adopted as the new surgical approach for the treatment of renal cell carcinoma. Laparoscopy offers the advantage of lower analgesic use, shorter hospital stay, and quicker recovery time. More recently, ablative technologies have been investigated as an alternative to laparoscopic partial nephrectomy. These techniques can often be performed percutaneously in the radiology suite, or laparoscopically without the need for hilar clamping. However, only the cryoablation and radiofrequency ablation modalities have had widespread use with several series reporting short to intermediate results. This review shows that both cryoablation and radiofrequency ablation are promising therapies in patients with small renal tumours (<4 cm), who are considered poor candidates for more involved surgery. OBJECTIVE: • To determine the current status of the literature regarding the clinical efficacy and complication rates of cryoablation vs radiofrequency ablation in the treatment of small renal tumours. METHODS: • A review of the literature was conducted. There was no language restriction. Studies were obtained from the following sources: MEDLINE, EMBASE and LILACS. • Inclusion criteria were (i) case series design with more than one case reported, (ii) use of cryoablation or radiofrequency ablation, (iii) patients with renal cell carcinoma and, (iv) outcome reported as clinical efficacy. • When available, we also quantified the complication rates from each included study. • Proportional meta-analysis was performed on both outcomes with a random-effects model. The 95% confidential intervals were also calculated. RESULTS: • Thirty-one case series (20 cryoablation, 11 radiofrequency ablation) met all inclusion criteria. • The pooled proportion of clinical efficacy was 89% in cryoablation therapy from a total of 457 cases. There was a statistically significant heterogeneity between these studies showing the inconsistency of clinical and methodological aspects. • The pooled proportion of clinical efficacy was 90% in radiofrequency ablation therapy from a total of 426 cases. There was no statistically significant heterogeneity between these studies. • There was no statistically significant difference regarding complications rate between cryoablation and radiofrequency ablation. CONCLUSIONS: • This review shows that both ablation therapies have similar efficacy and complication rates. • There is urgency for performing clinical trials with long-term data to establish which intervention is most suitable for the treatment of small renal masses.