Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

BACKGROUND: Growth hormone (GH)-secreting pituitary adenoma is a severe endocrine disease. Surgery is the currently recommended primary therapy for patients with GH-secreting tumours. However, non-surgical therapy (pharmacological therapy and radiation therapy) may be performed as primary therapy or may improve surgical outcomes. OBJECTIVES: To assess the effects of surgical and non-surgical interventions for primary and salvage treatment of GH-secreting pituitary adenomas in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases was 1 August 2022. We did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of more than 12 weeks' duration, reporting on surgical, pharmacological, radiation, and combination interventions for GH-secreting pituitary adenomas in any healthcare setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance, screened for inclusion, completed data extraction, and performed a risk of bias assessment. We assessed studies for overall certainty of the evidence using GRADE. We estimated treatment effects using random-effects meta-analysis. We expressed results as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) for continuous outcomes, or in descriptive format when meta-analysis was not possible. MAIN RESULTS: We included eight RCTs that evaluated 445 adults with GH-secreting pituitary adenomas. Four studies reported that they included participants with macroadenomas, one study included a small number of participants with microadenomas. The remaining studies did not specify tumour subtypes. Studies evaluated surgical therapy alone, pharmacological therapy alone, or combination surgical and pharmacological therapy. Methodological quality varied, with many studies providing insufficient information to compare treatment strategies or accurately judge the risk of bias. We identified two main comparisons, surgery alone versus pharmacological therapy alone, and surgery alone versus pharmacological therapy and surgery combined. Surgical therapy alone versus pharmacological therapy alone Three studies with a total of 164 randomised participants investigated this comparison. Only one study narratively described hyperglycaemia as a disease-related complication. All three studies reported adverse events, yet only one study reported numbers separately for the intervention arms; none of the 11 participants were observed to develop gallbladder stones or sludge on ultrasonography following surgery, while five of 11 participants experienced any biliary problems following pharmacological therapy (RR 0.09, 95% CI 0.01 to 1.47; 1 study, 22 participants; very low-certainty evidence). Health-related quality of life was reported to improve similarly in both intervention arms during follow-up. Surgery alone compared to pharmacological therapy alone may slightly increase the biochemical remission rate from 12 weeks to one year after intervention, but the evidence is very uncertain; 36/78 participants in the surgery-alone group versus 15/66 in the pharmacological therapy group showed biochemical remission. The need for additional surgery or non-surgical therapy for recurrent or persistent disease was described for single study arms only. Surgical therapy alone versus preoperative pharmacological therapy and surgery Five studies with a total of 281 randomised participants provided data for this comparison. Preoperative pharmacological therapy and surgery may have little to no effect on the disease-related complication of a difficult intubation (requiring postponement of surgery) compared to surgery alone, but the evidence is very uncertain (RR 2.00, 95% CI 0.19 to 21.34; 1 study, 98 participants; very low-certainty evidence). Surgery alone may have little to no effect on (transient and persistent) adverse events when compared to preoperative pharmacological therapy and surgery, but again, the evidence is very uncertain (RR 1.23, 95% CI 0.75 to 2.03; 5 studies, 267 participants; very low-certainty evidence). Concerning biochemical remission, surgery alone compared to preoperative pharmacological therapy and surgery may not increase remission rates up until 16 weeks after surgery; 23 of 134 participants in the surgery-alone group versus 51 of 133 in the preoperative pharmacological therapy and surgery group showed biochemical remission. Furthermore, the very low-certainty evidence did not suggest benefit or detriment of preoperative pharmacological therapy and surgery compared to surgery alone for the outcomes 'requiring additional surgery' (RR 0.48, 95% CI 0.05 to 5.06; 1 study, 61 participants; very low-certainty evidence) or 'non-surgical therapy for recurrent or persistent disease' (RR 1.22, 95% CI 0.65 to 2.28; 2 studies, 100 participants; very low-certainty evidence). None of the included studies measured health-related quality of life. None of the eight included studies measured disease recurrence or socioeconomic effects. While three of the eight studies reported no deaths to have occurred, one study mentioned that overall, two participants had died within five years of the start of the study. AUTHORS' CONCLUSIONS: Within the context of GH-secreting pituitary adenomas, patient-relevant outcomes, such as disease-related complications, adverse events and disease recurrence were not, or only sparsely, reported. When reported, we found that surgery may have little or no effect on the outcomes compared to the comparator treatment. The current evidence is limited by the small number of included studies, as well as the unclear risk of bias in most studies. The high uncertainty of evidence significantly limits the applicability of our findings to clinical practice. Detailed reporting on the burden of recurrent disease is an important knowledge gap to be evaluated in future research studies. It is also crucial that future studies in this area are designed to report on outcomes by tumour subtype (that is, macroadenomas versus microadenomas) so that future subgroup analyses can be conducted. More rigorous and larger studies, powered to address these research questions, are required to assess the merits of neoadjuvant pharmacological therapy or first-line pharmacotherapy.

A Comparative Assessment of Three Formulations of Botulinum Toxin Type A for Facial Rhytides: A Systematic Review with Meta-Analyses.

BACKGROUND: Three formulations of botulinum toxin are available for facial rhytides. It is unclear which formulation offers the greatest balance of benefits and harms. The objective of this study was to conduct a systematic review with meta-analyses to compare formulations of botulinum toxin for reduction of facial rhytides at the glabella. METHODS: The authors' protocol was registered with the International Prospective Register of Systematic Reviews (CRD4201200377). A systematic literature search was performed identifying double-blind studies. The authors assessed 1-, 3-, and 4-month follow-up. The authors performed pairwise meta-analyses using random effects models to compare response rates among the three botulinum formulations and a network meta-analysis. RESULTS: A total of 18 studies (3082 patients) were included. At 30-, 90-, and 120-day follow-up, all medications with available data showed statistically significantly increased treatment response versus placebo. Only high-dose onabotulinum toxin (compared to standard-dose onabotulinum toxin) offered additional benefit at 30 days. Exploratory analysis using network meta-analysis mostly suggested insufficient evidence of incremental benefits when comparing specific formulations. CONCLUSIONS: Evidence supporting benefits versus placebo of the different formulations was clear over time. Comparisons between active formulations were rare and typically based on single trials of small to moderate sample size. The data suggest some gains with high-dose onabotulinum toxin (relative to standard dose), whereas exploratory indirect comparisons between active formulations were largely associated with inconclusive findings. Future studies should undertake head-to-head comparisons of the different formulations and ensure longer follow-up to best inform the accumulating evidence base. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Anti-IgE monoclonal antibody therapy for the treatment of chronic rhinosinusitis: a systematic review.

BACKGROUND: Several options are available for the treatment of chronic rhinosinusitis (CRS), but disease control remains elusive for many patients. Recently, literature has emerged describing anti-IgE monoclonal antibody as a potential therapy for CRS. However, its effectiveness and safety are not well known. The purpose of this systematic review was to assess the effectiveness and safety of anti-IgE therapy and to identify evidence gaps that will guide future research for the management of CRS. METHODS: Methodology was registered with PROSPERO (No. CRD42014007600). A comprehensive search was performed of standard bibliographic databases, Google Scholar, and clinical trials registries. Only randomized controlled trials assessing anti-IgE therapy in adult patients for the treatment of CRS were included. Two independent reviewers extracted data using a pre-defined extraction form and performed quality assessment using the Cochrane risk of bias tool and the GRADE framework. RESULTS: Two studies met our inclusion criteria. When comparing anti-IgE therapy to placebo, there was a significant difference in Lund-McKay score (p = 0.04) while no difference was seen for percent opacification on computed tomography (CT). At 16 weeks, treatment led to a decrease in clinical polyp score. No significant difference was seen with regard to quality of life (Total Nasal Symptom Severity (TNSS), p < 0.21; Sinonasal Outcome Test 20 (SNOT-20), p < 0.60), and no serious complications were reported in either trial. Based on the quality assessment, studies were deemed to be of moderate risk of bias and a low overall quality of evidence. CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness of anti-IgE monoclonal antibody therapy for the treatment of CRS.

A comparative assessment of three formulations of botulinum toxin A for facial rhytides: a systematic review and meta-analyses.

BACKGROUND: Botulinum toxin A is a commonly used biological medication in the field of facial plastic surgery. Currently, there are three distinct formulations of botulinum toxin A, each with their purported benefits and advantages. However, there is considerable confusion as to the relative efficacy and side-effects associated with each formulation. Therefore, the purpose of this paper is to systematically assess published studies and perform a meta-analysis to determine if there is a significant advantage of any of the individual formulations. METHODS/DESIGN: A systematic literature search was performed for all relevant English language randomized controlled trials using Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. Inclusion criteria included any randomized controlled trial (RCT) that assessed the use of botulinum toxin for cosmetic purposes. The included articles were also analyzed for bias using the Cochrane Collaboration's tool for assessing the risk of bias in RCTs. DISCUSSION: The results of this review will provide clinicians with an unbiased, high level of evidence of the comparative efficacy of individual preparations of botulinum toxin A.