Pharmacological treatment is not very effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in the use of the multimodal analgesic approach. We performed a new independent review to assess whether more and better-quality evidence has become available since the last systematic review. We evaluated the efficacy, tolerability, and safety of double-blinded randomized controlled trials involving only adult participants and comparing combination therapy (CT: ≥2 drugs) with a placebo and/or at least one other comparator with an NP indication. The primary outcome assessed was the proportion of participants reporting ≥50% pain reductions from baseline. The secondary outcome assessed was the proportion of drop-outs due to treatment-emergent adverse events. After removing duplicates, 2323 citations were screened, with 164 articles assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only five lasted for at least 12 weeks and only six complied with the required data for complete analysis. CT has been adopted for years without robust evidence. Efforts have been made to achieve better-quality evidence, but the quality has not improved over the years. In this regard, guidelines for NP should attempt to make recommendations about CT research, prioritizing which combinations to analyze.

Purpose: Pylorus-preserving pancreatoduodenectomy (PPPD) has been the gold standard for pancreatic head lesion resection for several years. Some studies have noted that it involves more delayed gastric emptying (DGE) than classical Whipple (i.e., pancreatoduodenectomy with antrectomy). Our working hypothesis was that the classical Whipple has a lower incidence of DGE. We aimed to compare the incidence of DGE among pancreatoduodenectomy techniques. Methods: This pragmatic, randomized, open-label, single-center clinical trial involved patients who underwent classical Whipple (study group) or PPPD (control group). Gastric emptying was clinically evaluated using scintigraphy. DGE was defined according to the International Study Group of Pancreatic Surgery (ISGPS) criteria. The secondary endpoints were postoperative morbidity, length of hospital stay, anthropometric measurements, and nutritional status. Results: A total of 84 patients were randomized (42 per group). DGE incidence was 50% (20/40, 95% confidence interval (95% CI): 35–65%) in the study group and 62% (24/39, 95% CI: 46–75%) in the control group (p = 0.260). No differences were observed between both groups regarding postoperative morbidity or length of hospital stay. Anthropometric measurements at 6 months post-surgery: triceps fold measurements were 12 mm and 16 mm (p = 0.021). At 5 weeks post-surgery, triceps fold measurements were 13 mm and 16 mm (p = 0.020) and upper arm circumferences were 26 cm and 28 cm (p = 0.030). No significant differences were observed in nutritional status. Conclusion: DGE incidence and severity did not differ between classical Whipple and PPPD. Some anthropometric measurements may indicate a better recovery with PPPD. Trial registration: ClinicalTrials.gov Identifier: NCT03984734.

Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective–prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients’ cancer characteristics with pain, and then the association of patients’ pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases.

Background: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. Methods: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. Discussion: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz’s capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.

Introduction: Acute pancreatitis is a high-incidence benign disease. In 2009, it was the second highest cause of total hospital stays, the largest contributor to aggregate costs (approximately US$ 7000.00 per hospitalization), and the fifth leading cause of in-hospital deaths in the United States. Although almost 80% of acute pancreatitis cases are mild (usually requiring short-term hospitalization and without further complications), severe cases can be quite challenging. Classifications, scores, and radiological criteria have been developed to predict disease severity and outcome accurately; however, in-hospital care remains of widespread use, regardless of disease severity. A recent Turkish study reported that mild acute pancreatitis can be effectively and safely managed with home monitoring. Although the optimal timing for oral refeeding remains controversial and could cast some doubt on the feasibility of home monitoring, some guidelines already advocate for starting it within 24 hours. The present clinical trial aims to assess whether home monitoring is effective, safe and non-inferior to hospitalization for managing mild acute pancreatitis. Methods: This will be a multicenter open-label randomized (1:1) controlled clinical trial to assess the efficacy and safety of home monitoring compared to in-hospital care for mild acute pancreatitis. All patients coming to the emergency department with suspected acute pancreatitis will be screened for enrollment. The main variable will be treatment failure (Yes/No) within the first 7 days after randomization. Discussion: Acute pancreatitis implies a high economic burden in healthcare systems worldwide. Recent evidence suggests that mild disease can be safely and effectively treated with home monitoring. This approach may produce considerable cost savings and positively impact patients’ quality of life. We expect the results to show that home monitoring is effective and not inferior to hospitalization for managing mild acute pancreatitis and that the economic costs are lower, kickstarting similar trials throughout the world, optimizing the use of limited healthcare budgets, and improving patients’ quality of life.

Pharmacological treatment is not very effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in the use of the multimodal analgesic approach. We performed a new, independent review to assess whether more evidence and of better-quality has become available since the last systematic review. We evaluated the efficacy, tolerability, and safety of double-blinded, randomized, controlled trials involving only adult participants and comparing combination therapy (CT: ≥ 2 drugs) to a placebo and/or at least one other comparator with an NP indication. The primary outcome assessed was the proportion of participants reporting ≥50% pain reductions from baseline. The secondary outcome assessed was the proportion of drop-outs due to treatment-emergent adverse events. After removing duplicates, 2323 citations were screened, with 164 articles assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only five lasted for at least 12 weeks and only six complied with the required data for complete analysis. CT has been adopted for years without robust evidence. Efforts have been made to achieve better-quality evidence, but the quality has not improved over the years. In this regard, guidelines for NP should attempt to make recommendations about CT research, prioritizing which combinations to analyze.