Case report: A comatose patient with pregabalin overdose successfully treated with continuous renal replacement therapy.

Pregabalin (PB) overdose causes mild symptoms and coma is rarely seen unless the patient has also ingested sedatives and/or has preexisting renal disease. We present a case report of a suicide attempt with PB where the patient presented in a comatose state that was successfully treated with continuous renal replacement therapy (CRRT). Treatment of PB overdose is usually supportive. However, previous reports of PB overdose have been treated with intermittent hemodialysis (IHD) in patients with preexisting renal disease. The problem with IHD is that it is only available in specialist centers and unsuitable for unstable patients. In the following case report, the patient presented to the emergency department (ED) unconscious and hypotensive. It was thought that the patient tried to commit suicide by taking an overdose of zopiclone tablets, as empty packets of zopiclone tablets were found beside the patient. There was no effect with flumazenil treatment, so the patient was intubated, mechanically ventilated, and admitted to the intensive care unit (ICU) where inotropic support was started. Despite supportive therapy, there was no improvement in the patient's condition. Further investigation into the patient's medical records uncovered prescriptions of PB. Based on this finding, plasma PB levels were measured and found to be 20 times the upper limit of the therapeutic reference range. CRRT was instituted and after 6 h of treatment the patient woke up. Hospitals with ICUs often have CRRT available in their units whereas IHD is less readily available. This case report demonstrates that CRRT is an effective method for treating PB overdose in an unconscious unstable patient that was unsuitable for transfer to another hospital.

Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials.

The efficacy and safety of semaglutide vs comparators in non-elderly (<65 years) and elderly (≥65 years) patients with type 2 diabetes (T2D) across the SUSTAIN 1-5 trials were evaluated. Patients were randomized to once-weekly subcutaneous semaglutide (0.5 or 1.0 mg) vs placebo, sitagliptin, exenatide or insulin. The primary objective was change in HbA1c and secondary objectives were changes in body weight and safety. Mean HbA1c decreased from baseline by 1.2%-1.5% and 1.5%-1.9% vs 0%-0.9% (non-elderly, n = 3045) and by 1.3%-1.5% and 1.2%-1.8% vs 0.2%-1.0% (elderly, n = 854) with semaglutide 0.5 and 1.0 mg vs comparators. Similar reductions from baseline in mean body weight with semaglutide occurred in both age groups. Similar proportions of patients experienced adverse events; premature treatment discontinuations were higher in elderly vs non-elderly patients. No increased risk of severe or blood glucose-confirmed hypoglycaemia was seen with semaglutide vs comparators between age groups. Semaglutide had a comparable efficacy and safety profile in non-elderly and elderly patients across the SUSTAIN 1-5 trials, making it an effective treatment option for elderly patients with T2D.

Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial.

Context: Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. Objective: To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. Design: Phase 3a, double-blind, placebo-controlled, 30-week trial. Setting: This study included 90 sites in five countries. Patients: We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. Interventions: Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. Main Outcome Measures: Primary endpoint was change in glycated Hb (HbA1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. Results: At week 30, mean HbA1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. Conclusions: Semaglutide, added to basal insulin, significantly reduced HbA1c and body weight in patients with uncontrolled T2D vs placebo.

Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy.

AIMS: To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme. MATERIALS AND METHODS: The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2-year, pre-approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at-risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage-points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC. RESULTS: There was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre-existing DR and poor glycaemic control at baseline, and who were treated with insulin. CONCLUSIONS: Early worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide.

Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block proposes to block these nerves and has provided pain relief for patients undergoing breast cancer surgery, but has yet to be evaluated in patients with PPBCS. METHODS: The aim of this pilot study was to examine the effects of the Pecs block on summed pain intensity (SPI) and sensory function (through quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. RESULTS: Patients experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. CONCLUSIONS: This pilot study suggests that the pectoral nerves play a role in the maintenance of pain in the breast area in PPBCS and begs for further research.

Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) affects 25 - 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. OBJECTIVES: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. STUDY DESIGN: This prospective pilot study was performed in 2 parts: Part 1 determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. SETTING: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. METHODS: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic ultrasonography to establish the sonoanatomy of the ICBN. Part 2: Six patients with PPBCS who had pain in the axilla and upper arm were recruited for the study. Summed pain intensity (SPI) scores and sensory function were measured before and 30 minutes after the block was administered. SPI is a combined pain score of numerical rating scale (NRS) at rest, movement, and 100kPa pressure applied to the maximum point of pain using pressure algometry (max = 30). Sensory function was measured using quantitative sensory testing, which consisted of sensory mapping, thermal thresholds, suprathreshold heat pain perception as well as heat and pressure pain thresholds. The ICBN block was performed under ultrasound guidance and 10 mL 0.5% bupivacaine was injected. OUTCOME ASSESSMENT: The ability to perform the ICBN block and its analgesic and sensory effects. RESULTS: Only the second intercostal space could be seen on ultrasound which was adequate to perform the ICBN block. The mean difference in SPI was -9 NRS points (95%CI: -14.1 to -3.9), P = 0.006. All patients had pre-existing areas of hypoesthesia which decreased in size in 4/6 patients after the block. LIMITATIONS: The main limitation of this pilot study is its small sample size, but despite this, a statistically significant effect was observed. CONCLUSION: We have successfully managed to block the ICBN using ultrasound guidance and demonstrated an analgesic effect in patients in PPBCS calling for placebo-controlled studies.

Neural blockade for persistent pain after breast cancer surgery.

Persistent pain after breast cancer surgery is predominantly a neuropathic pain syndrome affecting 25% to 60% of patients and related to injury of the intercostobrachial nerve, intercostal nerves, and other nerves in the region. Neural blockade can be useful for the identification of nerves involved in neuropathic pain syndromes or to be used as a treatment in its own right. The purpose of this review was to examine the evidence for neural blockade as a potential diagnostic tool or treatment for persistent pain after breast cancer surgery. In this systematic review, we found only 7 studies (n = 135) assessing blocks directed at 3 neural structures-stellate ganglion, paravertebral plexus, and intercostal nerves-but none focusing on the intercostobrachial nerve. The quality of the studies was low and efficacy inconclusive, suggesting a need for well-designed, high-quality studies for this common clinical problem.