Antiresorptive treatments for corticosteroid-induced osteoporosis: a Bayesian network meta-analysis.

INTRODUCTION: Corticosteroid-induced osteoporosis (CIO) is the most common type of secondary osteoporosis, leading to fractures, and increased morbidity and mortality. SOURCE OF DATA: Pubmed, EMBASE, Scopus and Google Scholar databases. AREAS OF AGREEMENT: Prolonged glucocorticoids administration leads to secondary osteoporosis. AREAS OF CONTROVERSY: The optimal management for CIO is controversial. GROWING POINTS: The present study compared bone mineral density, fractures and adverse events in patients undergoing treatment with risedronate, alendronate, zoledronate, denosumab or etidronate for CIO. AREAS TIMELY FOR DEVELOPING RESEARCH: For selected patients with CIO, alendronate performed better overall. These results must be interpreted within the limitations of the present study. LEVEL OF EVIDENCE: I, Bayesian network meta-analysis of randomized clinical trials.

Placebo effect in pharmacological management of fibromyalgia: a meta-analysis.

INTRODUCTION: The management of fibromyalgia involves a combination of pharmacological and non-pharmacological treatments. SOURCE OF DATA: Recently published literature in PubMed, Google Scholar and Embase databases. AREAS OF AGREEMENT: Several pharmacological and non-pharmacological strategies have been proposed for the management of fibromyalgia. However, the management of fibromyalgia remains controversial. The administration of placebo has proved to be more effective than no treatment in many clinical settings and evidence supports the 'therapeutic' effects of placebo on a wide range of symptoms. AREAS OF CONTROVERSY: The placebo effect is believed to impact the clinical outcomes, but its actual magnitude is controversial. GROWING POINTS: A meta-analysis comparing pharmacological management versus placebo administration for fibromyalgia was conducted. AREAS TIMELY FOR DEVELOPING RESEARCH: Drug treatment resulted to be more effective than placebo administration for the management of fibromyalgia. Nevertheless, placebo showed a beneficial effect in patients with fibromyalgia. Treatment-related adverse events occurred more frequently in the drug treatment. LEVEL OF EVIDENCE: I, Bayesian network meta-analysis of double-blind randomized clinical trials.

Short stems for total hip replacement among middle-aged patients.

INTRODUCTION: The purpose of the present study was to investigate the role of short stem implants for primary total hip arthroplasty in middle-aged patients. For this purpose, a meta-analysis of the current literature was conducted. The focus was on clinical outcomes,radiological parameters, and further complications of both components. MATERIAL AND METHODS: The study was performed according to the PRISMA guidelines. All randomized and non-randomized clinical trials comparing short stem versus standard stem prostheses for THA were considered for inclusion. Only studies reporting data concerning uncemented stems for primary total hip arthroplasty were included. Only studies reporting data concerning patients with a mean age of 45 to 69 were included. RESULTS: A total of 2197 procedures in 2116 patients were analysed. The mean follow-up was 30.2 months. The short stem group showed a statistically significant higher WOMAC score and a reduced total estimated blood loss compared with the standard stem group. The short stem group showed a reduced rate of femoral fractures, dislocations, and revision, but without statistical significance. CONCLUSIONS: According to the main findings of this meta-analysis and current evidence, we encourage the use of the uncemented short stems during primary total hip arthroplasty in middle-aged patients.

Single- versus double-bundle patellar graft insertion for isolated MPFL reconstruction in patients with patellofemoral instability: a systematic review of the literature.

INTRODUCTION: The MPFL reconstruction is performed either via a single-bundle (SB) or double-bundle (DB) procedure. The purpose of this study is to perform a systematic review comparing SB versus DB graft for recurrent patellofemoral instability, to summarize current evidence, and to clarify the role of both techniques. We focused on clinical scores, physical examination, complications, revision surgeries, and failures. MATERIAL AND METHODS: In May of 2019 the main online databases were accessed. All the clinical studies treating isolated MPFL reconstruction for patellofemoral instability through a single and/or double-bundle graft were enrolled in the present systematic review. Only articles reporting primary isolated MPFL reconstruction, reporting a minimum of 12-months follow-up were considered for inclusion. RESULTS: The scores of interest were in favour of the DB cohort: Kujala (+ 3.2, P = 0.03), Lysholm (+ 5.1, P = 0.001), Tegner (+ 0.3, P = 0.2), IKDC (+ 5.4, P = 0.01), VAS (+ 0.8, P = 0.3), ROM (+ 9.96, P = 0.04). In the DB graft, a reduction of overall complications (OR 0.59; P = 0.1), further surgeries (OR 0.64; P = 0.12) and re-dislocations (OR 0.61; P = 0.16) was observed. The SB group reported a reduction in the post-operative apprehension test (OR 2.42; P = 0.24). CONCLUSION: Current study support the use of double-bundle tendon graft for isolated MPFL reconstruction in selected patients with recurrent patellofemoral instability.

Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up: a systematic review of the literature.

PURPOSE: According to the World Health organization (WHO), more than 10% in people older than 60 years suffer from osteoarthritis (OA). Over the last years, there has been an increased interest around regenerative medicine, especially regarding stem cell treatments and related applications. We hypothesize that stem cell therapies can represent a feasible option for idiopathic knee OA, delaying or even avoiding the joint replacement. To emphasize the potential of percutaneous injections of mesenchymal stem cells for knee OA, a comprehensive systematic review of the literature was conducted. MATERIAL AND METHODS: Two independent authors (FM, GC) performed the literature search. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The main databases were accessed: Pubmed, Embase, Google Scholar, Cochrane Systematic Reviews, Scopus, AMED. For this systematic review, all articles treating percutaneous injections of mesenchymal stem cells for knee OA were considered. Because of the rapid advancements promoted by the scientific progress on stem cell expansion and processing, only articles published within the last five years were included. Solely articles reporting the outcomes of interest across 6- and 12-month follow-up were recruited for eligibility. We included only studies reporting quantitative data under the outcomes of interest. We referred for the quality assessment to the Coleman Methodology Score (CMS). The statistical analysis was performed with Review Manager Software 5.3 (The Nordic Cochrane Centre, Copenhagen). RESULTS: A total of 18 studies were enrolled in the present study, comprising 1069 treated knees. The mean age of the samples was 57.39 ± 7.37 years. 72% of the included studies harvested the stem cells from the iliac crest (bone marrow-derived MSCs), the remaining 28% from the adipose tissue (adipose-derived MSCs). The mean visual analogic scale improved from 18.37 to 30.98 and 36.91 at 6- and 12-month follow-up, respectively. The mean WOMAC score improved from 25.66 to 25.23 and 15.60 at 6- and 12-month follow-up, respectively. The mean walking distance improved from 71.90 to 152.22 and 316.72 at 6- and 12-month follow-up, respectively. The mean Lequesne scale improved from 33.76 to 12.90 at 12-month follow-up. The KOOS score improved from 41.07 to 8.47% and 18.94 at 6- and 12-month follow-up. All the KOOS subscales improved significantly from the baseline. A total of 136 (12.7%) local complications were detected. CONCLUSION: According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes, regardless of the cell source. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life.

Bipolar versus monopolar hemiarthroplasty for displaced femur neck fractures: a meta-analysis study.

INTRODUCTION: Hemiarthroplasty is commonly performed to treat femoral neck fractures. Still, there is a lack of consensus concerning the best component for hemiarthroplasty: unipolar and bipolar implants. Last meta-analysis on this topic is outdated, and an update of current evidences is required. The purpose of this study is to conduct a meta-analysis comparing the unipolar versus bipolar implants for hemiarthroplasty, focusing on the clinical scores, perioperative data, further complications and mortality rate. MATERIALS AND METHODS: In September 2019, the main databases were accessed: all the clinical trials comparing unipolar versus bipolar hemiarthroplasty for displaced femoral neck fractures were considered for inclusion. For the methodological quality assessment, we referred to the PEDro score. For the statistical analysis, we referred to the Review Manager 5.3 (The Nordic Cochrane Collaboration, Copenhagen). For implant survivorship, we referred to the STATA/MP software version 14.1 (StataCorp, College Station, Texas). RESULTS: A total of 27 articles were considered for inclusion, consisting of 16 randomized and 11 non-randomized clinical trials. A total of 4511 patients were enrolled, undergoing a mean 21.26 months follow-up. A statistically significant reduction in the acetabular erosion was observed in the bipolar group (OR 3.16, P < 0.0001). Although statistically insignificant, the bipolar group reported a reduction in the mean Harris hip score, reduced surgical duration and hospitalization, reduced dislocation and revisions rate. Concerning the mortality, a reduction across all the follow-ups in favor of the bipolar group was detected, but without statistically significance. CONCLUSIONS: This meta-analysis evidenced a reduction in the acetabular erosion after bipolar hemiarthroplasty compared to the unipolar implants. Any statistically significant difference concerning the other endpoints of interest was detected. Current evidence concerning this topic are controversial, and further randomized clinical trials are required.

Duloxetine for fibromyalgia syndrome: a systematic review and meta-analysis.

INTRODUCTION: The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated. MATERIAL AND METHODS: This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered. RESULTS: Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m2. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed. CONCLUSIONS: Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.

Conventional Prostheses versus Sutureless Perceval for Aortic Valve Replacement: A Meta-Analysis.

PURPOSE: Perceval sutureless valves have gained popularity. Whether this implant performs superior to the traditional sutured prosthesis remains unclear. This meta- analysis compared the Perceval implants versus the sutured conventional valves for aortic valve replacement (AVR). METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were accessed: PubMed, Google Scholar, Web of Science, Scopus, and EMBASE. All clinical investigations comparing Perceval versus the conventional prostheses for AVR were considered. RESULTS: The Perceval group demonstrated higher rate of pacemaker implantation (P <0.00001). Aortic cross-clamp (ACC) time (P <0.00001) and cardiopulmonary bypass (CPB) time (P <0.00001) were shorter in the Perceval group. Similarity was found in mean and peak pressure gradient (P = 0.8 and P = 0.2, respectively), mean aortic valve area (P = 0.3), length of intensive care unit (P = 0.4) and hospital stay (P = 0.2), rate of revision (P = 0.11), hemorrhages (P = 0.05), paravalvular leak (P = 0.3), cerebrovascular complication (P = 0.7), and early mortality (P = 0.06). CONCLUSION: Given the shorter ACC time and CPB time, Perceval AVR can be an alternative in high-risk patients. The higher rate of pacemaker implantation following Perceval may limit its routine implantation.

Pregabalin administration in patients with fibromyalgia: a Bayesian network meta-analysis.

Several studies investigated the effectiveness and the safety of different doses of pregabalin in fibromyalgia. However, the optimal protocol remains controversial. A Bayesian network meta-analysis comparing 300, 450, and 600 mg/daily of pregabalin for fibromyalgia was conducted. The literature search was conducted in January 2022. All the double-blind randomised clinical trials comparing two or more dose protocols of pregabalin for fibromyalgia were accessed. Studies enrolling less than 50 patients were not eligible, nor were those with a length of follow-up shorter than eight weeks. The outcomes of interests were: Fibromyalgia Impact Questionnaire (FIQ), sleep quality, and adverse events. The network meta-analyses were performed using the routine for Bayesian hierarchical random-effects model analysis, with log odd ratio (LOR) and standardized mean difference (SMD) effect measure. Data from 4693 patients (mean age 48.5 years) were retrieved. 93.1% (4370 of 4693 patients) were women. The median follow-up was 14.8 weeks. Pregabalin 450 mg/daily resulted in greater reduction in Fibromyalgia Impact Questionnaire (SMD - 1.83). Pregabalin 600 demonstrated the greatest sleep quality (SMD 0.15). Pregabalin 300 mg/daily evidenced the lowest rate of adverse events (LOR 0.12). The dose of pregabalin must be customised according to patients' characteristics and main symptoms.

Pharmacological management of fibromyalgia: a Bayesian network meta-analysis.

INTRODUCTION: The identification of the most effective therapy for patients with fibromyalgia (FM) remains controversial. Thus, we conducted a Bayesian network meta-analysis to compare several drugs employed as pharmacological management for FM. AREAS COVERED: The following databases were accessed in October 2021: PubMed, Google Scholar, Embase, and Scopus. All the randomized clinical trials (RCTs) that compare two or more pharmacological management for fibromyalgia were accessed. Only studies involving a minimum of 10 patients with a length of follow-up longer than 4 weeks were included. The data from the fibromyalgia impact questionnaire (FIQ) and the physical and mental subscales short form 36 (SF36) were extracted at last follow-up. Additionally, the number of adverse events leading to the study of discontinuation was extracted. The compounds of interests were duloxetine, pregabalin, fluoxetine, gabapentin, milnacipran, trazodone, placebo, nortriptyline, IGF-I, amitriptyline, and the combination of fluoxetine and amitriptyline, pregabalin, and trazodone. EXPERT OPINION: According to published evidence, pregabalin, and duloxetine evidenced the greatest improvement of the FIQ and SF36 Physical and Mental subscales, along with the lowest rate of adverse events leading to study discontinuation. The results must be interpreted in light of possible adverse events associated with the use of these drugs.

Superior outcomes with Argatroban for heparin-induced thrombocytopenia: a Bayesian network meta-analysis.

Background Argatroban, lepirudin, desirudin, bivalirudin, and danaparoid are commonly used to manage heparin-induced thrombocytopenia related complications. However, the most suitable drug for this condition still remains controversial. Aim of the review This Bayesian network meta-analysis study compared the most common anticoagulant drugs used in the management of heparin-induced thrombocytopenia. Method All clinical trials comparing two or more anticoagulant therapies for suspected or confirmed heparin-induced thrombocytopenia were considered for inclusion. Studies concerning the use of heparins or oral anticoagulants were not considered. Data concerning hospitalisation length, thromboembolic, major, and minor haemorrhagic events, and mortality rate were collected. The network analyses were made through the STATA routine for Bayesian hierarchical random-effects model analysis with standardised mean difference (SMD) and log odd ratio (LOR) effect measures. Results Data from a total of 4338 patients were analysed. The overall mean age was 62.31 ± 6.6 years old. Hospitalization length was considerably shorter in favour of the argatroban group (SMD: - 1.70). Argatroban evidenced the lowest rate of major (LOR: - 1.51) and minor (LOR: - 0.57) haemorrhagic events. Argatroban demonstrated the lowest rate of thromboembolic events (LOR: 0.62), and mortality rate (LOR: - 1.16). Conclusion Argatroban performed better overall for selected patients with HIT. Argatroban demonstrated the shortest hospitalization, and lowest rate of haemorrhages, thromboembolisms, and mortality compared to bivalirudin, lepirudin, desirudin, and danaparoid.

BMI but not age and sex negatively impact on the outcome of pharmacotherapy in fibromyalgia: a systematic review.

INTRODUCTION: The impact of sex, age, body mass index (BMI) in fibromyalgia is still unclear. A systematic review was conducted to investigate whether sex, age and BMI influence the clinical outcomes and rate of adverse events. METHODS: The present study was performed according to the PRISMA guidelines. The literature search was performed in February 2021. All the RCTs investigating pharmacological strategies for fibromyalgia were accessed. RESULTS: Data from 51 RCTs (17,311 patients) were collected. Short Form 36 emotional, Social function and physical role subscales showed evidence of a negative association with BMI (P = 0.02, P = 0.002 and P = 0.0001, respectively). Depression and anxiety subscales of the Hospital Anxiety and Depression score demonstrated evidence of a positive association with age (P = 0.04 and P = 0.001, respectively) and sex (P = 0.00005 and P = 0.0001, respectively). Visual analog scale evidenced a positive association with BMI (P = 0.04). Clinical Global Impression Severity scale demonstrated evidence of a negative association with BMI (P = 0.02). CONCLUSION: Irrespective from the pharmacological approach, a higher BMI is negatively associated with a favorable outcome in patients with fibromyalgia. The association with sex and age remains controversial. LEVEL OF EVIDENCE: I, systematic review of RCTs.

Effect of drugs on bone mineral density in postmenopausal osteoporosis: a Bayesian network meta-analysis.

BACKGROUND: Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density. METHODS: The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis. RESULTS: Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD -0.220; SE 3.379), followed by pamidronate (SMD -5.662; SE 2.635) and zoledronate (SMD -10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD -0.256; SE 3.184), followed by alendronate (SMD -17.032; SE 3.191) and ibandronate (SMD -17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD -16.030; SE 1.702) and ibandronate (SMD -17.000; SE 1.679). CONCLUSION: Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD. LEVEL OF EVIDENCE: Level I, Bayesian network meta-analysis of RCTs.

Pharmacological Management of Postmenopausal Osteoporosis: a Level I Evidence Based - Expert Opinion.

Objectives: Postmenopausal osteoporosis carries a high risk of fractures, which decrease quality of life and are associated with high morbidity, mortality, and economic burden. The best pharmacological treatment options to manage and prevent osteoporotic fractures remain still unclear. The present study investigated the efficacy and safety of the most commonly employed drugs in the management of postmenopausal osteoporosis. Methods: Only RCTs comparing different drugs for the management of postmenopausal osteoporosis were included. Data from 76 RCTs (205,011 patients) were collected. The mean follow-up was 27.6 ± 14.9 months. Results: Denosumab reported the lowest rate of non-vertebral fractures (LOR -1.57), Romosozumab the lowest rate of vertebral fractures (LOR 1.99), and Ibandronate the lowest rate of hip fractures (LOR0.18). Serious adverse events resulted in the lowest in the Raloxifene group (LOR 3.11), while those leading to study discontinuation were lowest in the Romosozumab cohort (LOR 2.65). Conclusions: Denosumab resulted in most effective, particularly in reducing the occurrence of non-vertebral fractures. Romosozumab and Ibandronate resulted best to prevent, respectively, vertebral fractures and hip fractures. Adverse events leading to study discontinuation were less frequent in the Romosozumab and Denosumab groups, while Raloxifene and Alendronate showed a lower incidence of serious adverse events overall. Level of evidence: I, Bayesian network meta-analysis of RCTs.

Prognostic factors for patients with heparin-induced thrombocytopenia: a systematic review.

Background  Little is known with regards to the prognostic factors for patients with suspected or diagnosed Heparin-Induced Thromobocytopenia (HIT). The role of patient and therapy characteristics may play a role in predicting the outcome. Aim of the review To investigate the role of patient and therapy characteristics as potential prognostic factors for HIT-related complications (haemorrhagic and thromboembolic events), and mortality. Method The present systematic review was conducted according to the PRISMA statement. In September 2020, the main online databases were accessed: Pubmed, EMBASE, Scopus, Google Scholar. All the clinical trials concerning the management of patients with suspected or confirmed HIT were eligible. Studies evaluating the use of oral anticoagulants (e.g. vitamin K antagonists, Apixaban) were not considered, along with those comparing the use of heparin. For pairwise correlation, the Pearson Product-Moment Correlation Coefficient (r) was used. The final effect was evaluated according to the Cauchy-Schwarz inequality.Results Data from 33 clinical studies (4338 patients) were retrieved. The overall mean age was 62.3 ± 6.6 years old. Patients with HIT-related thromboembolism at the moment of diagnosis were associated with greater rate of haemorrhages (P > 0.0001), thromboembolism (P > 0.0001) and mortality (P = 0.001). Patients with more comorbidities at diagnosis were associated with a greater risk of haemorrhages (P = 0.07), thromboembolism (P = 0.002) and mortality (P = 0.002). Patients with longer duration of the therapy were associated with lower rate of mortality (P = 0.04). ConclusionsPatient comorbidities, presence of HIT-related thromboembolism on admission and shorter anticoagulant therapy were found to be negative prognostic factors. Thrombocythemia on admission, patients age and gender did not influence the overall outcome.