Pamidronate disodium 90mg powder and solvent for solution for infusion vials

BackgroundPeople with advanced chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT) refractory to medical therapy often require surgical parathyroidectomy. Severe and prolonged hypocalcemia immediately following parathyroidectomy for sHPT is often termed "hungry bone syndrome" (HBS).ObjectiveTo systematically review the effect of pre-operative interventions on post-operative hypocalcemia, HBS, and other related outcomes in patients with CKD and sHPT undergoing parathyroidectomy.DesignThis is a systematic review study.SettingDiverse study designs conducted in any country.PatientsAdult patients with CKD complicated by sHPT undergoing parathyroidectomy.MeasurementsPost-operative hypocalcemia, HBS, symptomatic hypocalcemia, and other related outcomes.MethodsWe searched Ovid MEDLINE, Embase, and Cochrane Controlled Trials Registry from inception until June 2024 for trials and observational studies of adults with CKD and sHPT that evaluated pre-operative interventions aimed at reducing the risk of hypocalcemia following parathyroidectomy. After 2 phases of study screening conducted in duplicate, we extracted data on study design, patient characteristics, interventions, and outcomes. Hypocalcemia was defined as serum calcium ResultsWe identified 3616 studies; 35 underwent full-text review, and 9 met final eligibility criteria. Interventions included pre-operative calcitriol (n = 2), pre-operative cinacalcet (n = 3), pre-operative alkaline phosphatase (ALP) measurement to guide intravenous (IV) calcium administration (n = 3), and pre-operative pamidronate (n = 1). All studies reported on at least one of: median/mean post-operative calcium (n = 7), incidence of post-operative hypocalcemia (n = 3), HBS (n = 1), and symptomatic hypocalcemia (n = 4). Interventions that reported on the risk of post-operative hypocalcemia included pre-operative pamidronate (n = 1, 37 participants, odds ratio [OR] = 0.003, 95% confidence interval [CI] = 0.000-0.072) and IV calcium guided by pre-operative ALP (n = 1, 271 participants, OR = 0.292, 95% CI = 0.175-0.488). There were insufficient data to meta-analyze study-specific effects for any intervention or outcome.LimitationsOur study was limited by significant heterogeneity in outcome reporting, which resulted in substantial outcome reporting bias and prevented pooled analyses. Furthermore, no randomized control trials met our inclusion criteria, which limited assessment of publication bias.ConclusionsPre-operative risk factors for HBS have been established in patients with CKD undergoing parathyroidectomy. However, limited research has evaluated pre-operative interventions to reduce the risk of HBS, and due to heterogeneity in outcome reporting across studies, there is still uncertainty about the effectiveness of such interventions. These findings support the need for future clinical trials.

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Background: The clinical definition of Ventilator Associated Pneumonia (VAP) is infection arising during intubation. The topic has attracted considerable interest as a subject of clinical efficacy research. Cost is an important factor when we consider similar options of antibiotic treatments. This study aims to review pharmacoeconomic evaluations made of different VAP treatments and summarize the evaluation methods utilized. Methods: : A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The search strategy was created considering the “PICOS” question, and data was sourced from PubMed, LILACS, Web of Science and Scopus databases, on October 2022. Inclusion and exclusion criterials were applied to filter the results. Findings: The search resulted in 574 studies, of which 12 were used. Of these, four studies evaluated empirical therapy. Antibiotic analysis was performed in eight case studies of Gram-negative infections and four of Gram-positive spectrum. The most prevalent analysis mode was Cost-effectiveness. Cost-minimization, Cost-benefit and general costs comparison were also seen. Different modellings were applied when performing the pharmacoeconomic analysis, such as Tree decision, Markov cohort, as well as methodologies like discrete event micro simulation and sequential simulation. Monte Carlo simulation was then used in five studies to analyze model sensitivity. The Linezolid treatment was shown to be more cost-effective than vancomycin in MRSA pneumonia. Doripinem also showed similar behavior when compared to imipinem in all included studies. Ceftazidime-avibactam and ceftalozane-tazobactam presented an advantage in cost-effectiveness when compared with meropenem. Clarithromycin and ceftriaxone+sulbactam+disodiumedetate used in adjuvant treatments, promoted reduction of the costs in patients with A. baumannii . Meropenem-varbobactam was also found to be a cost-effective treatment option when compared with standard therapies used in patients with CRE-KPC infections. Conclusion: Even though many models were used in pharmacoeconomic evaluations for VAP, Cost-effectiveness was clearly the most prevalent one. In short, the studies showed an advantage when using new medications. Nonetheless, we must be cautious when interpreting such findings, since they reflect a different reality for each country. Long-term impact and resource availability should also be considered.

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BackgroundMalignant bone tumors are one of the most painful types of cancer, and their pain is very difficult to manage. Pain-relieving methods such as radiotherapy, Bone-Modifying Agents (BMAs), and radiopharmaceuticals have been explored in different studies and found to be effective pain control measures and also prevention of skeletal-related events (SREs). This meta-analysis analyzes the global burden of pain in malignant bone tumors with an emphasis on severity, health outcomes, and the efficacy of pain management interventions.MethodsNineteen randomized controlled trials and comparative studies were selected, which included patients with Malignant Bone Tumors. Treatments involved External Beam Radiotherapy (EBRT) in single or multi-fractions, BMAs (zoledronic acid, ibandronate, pamidronate, denosumab), and radiopharmaceuticals (Radium-223, Strontium-89, Samarium-153) either alone or in combination. Random-effects models were used to compute standardized mean differences (SMDs), with the evaluation of heterogeneity, Jadad score, and GRADE quality.ResultsInterventions across all subgroups were effective at relieving pain and protecting bones. One-time EBRT was shown to be as effective as standard multi-fraction treatments (SMD 0.04, 95% CI -0.02-0.1) for pain management. BMA-based treatments yielded contradictory results: denosumab versus zoledronic acid did not show a significant difference (SMD 0.01, 95% CI -0.02-0.05), whereas bisphosphonates alone resulted in a significant uplift (SMD 0.12, 95% CI 0.05-0.2, pConclusionsRadiotherapy, BMAs, and radiopharmaceuticals, either singly or in tandem, are well-tolerated for managing pain and preventing SREs in patients with malignant bone tumors, thereby providing patients with various ways to enhance their quality of life.

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ObjectiveModic type 1 (MC-1) vertebral endplate changes are associated with chronic low back pain (LBP) and often reflect an inflammatory process. Pamidronate has demonstrated analgesic effects in conditions involving bone marrow oedema. Our study aimed to evaluate the efficacy of intravenous pamidronate in patients with inflammatory-like LBP and MRI-confirmed MC-1 changes.MethodIn the PEPTIDE study, a single-centre, randomised, double blind, placebo-controlled trial, adults aged 18-60 years with chronic inflammatory-like LBP unresponsive or intolerant to NSAIDs, and MRI-confirmed MC-1 were randomised (1:1) to receive either two consecutive daily infusions of pamidronate (90 mg) or placebo. The primary endpoint was the change in LBP intensity (VAS pain) after 3 months. Secondary outcomes included functional disability, quality of life, inflammatory symptoms, and analgesic consumption.ResultsForty-four participants (mean age 49.4 ± 8.9 years; 57% women) were randomised. At 3 months, the between-group difference in VAS pain reduction was not significant (difference -6.4 mm; 95%CI: -22.0 to 9.3). At 6 weeks, there was a trend toward pain improvement with pamidronate (difference -14.15 mm; 95% CI -28.85 to 0.55). Significantly more patients in the pamidronate group achieved predefined pain improvement thresholds, although this effect was not maintained at 3 or 6 months. Adverse events occurred more frequently in the pamidronate group (54.6% vs 27.3%), primarily flu-like symptoms.ConclusionThese findings are consistent with previous studies suggesting that bisphosphonates may provide a transient analgesic effect at 6 weeks but do not confer sustained clinical benefit at 3 or 6 months in MC-1-associated low back pain.

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