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Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceed the cons.

In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i) mechanical and thermal sensory alterations, (ii) responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii) the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT). SCT was performed at thoracic T8-T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm2) cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT- versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury) and glial activation markers (OX-42, GFAP, P2×4, P2×7, TLR4) was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1β, IL-6 and TNF-α were also markedly but differentially up-regulated at T6-T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p.), morphine (3-10 mg/kg s.c.) and tapentadol (10-20 mg/kg i.p.) significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a reliable model for testing innovative therapies aimed at reducing spinal cord lesion-induced central neuropathic pain.

Home treatment has been proposed as an alternative to acute in-patient care for mentally ill patients. However, there is only moderate evidence in support of home treatment. To test whether and to what degree home treatment services would enable a reduction (substitution) of hospital use. A total of 707 consecutively admitted adult patients with a broad spectrum of mental disorders (ICD-10: F2-F6, F8-F9, Z) experiencing crises that necessitated immediate admission to hospital, were randomly allocated to either a service model including a home treatment alternative to hospital care (experimental group) or a conventional service model that lacked a home treatment alternative to in-patient care (control group) (trial registration at ClinicalTrials.gov: NCT02322437). The mean number of hospital days per patient within 24 months after the index crisis necessitating hospital admission (primary outcome) was reduced by 30.4% (mean 41.3 v. 59.3, P<0.001) when a home treatment team was available (intention-to-treat analysis). Regarding secondary outcomes, average overall treatment duration (hospital days + home treatment days) per patient (mean 50.4 v. 59.3, P = 0.969) and mean number of hospital admissions per patient (mean 1.86 v. 1.93, P = 0.885) did not differ statistically significantly between the experimental and control groups within 24 months after the index crisis. There were no significant between-group differences regarding clinical and social outcomes (Health of the Nation Outcome Scales: mean 9.9 v. 9.7, P = 0.652) or patient satisfaction with care (Perception of Care questionnaire: mean 0.78 v. 0.80, P = 0.242). Home treatment services can reduce hospital use among severely ill patients in acute crises and seem to result in comparable clinical/social outcomes and patient satisfaction as standard in-patient care.

Acute kidney injury (AKI) complicates the clinical course of hospitalized patients by increasing need for intensive care treatment and mortality. There is only little data about its impact on AML patients undergoing intensive induction chemotherapy. In this study, we analyzed the incidence as well as risk factors for AKI development and its impact on the clinical course of AML patients undergoing induction chemotherapy. We retrospectively analyzed data from 401 AML patients undergoing induction chemotherapy between 2007 and 2019. AKI was defined and stratified according to KIDGO criteria by referring to a defined baseline serum creatinine measured on day 1 of induction chemotherapy. Seventy-two of 401 (18%) AML patients suffered from AKI during induction chemotherapy. AML patients with AKI had more days with fever (7 vs. 5, p = 0.028) and were more often treated on intensive care unit (45.8% vs. 10.6%, p < 0.001). AML patients with AKI had a significantly lower complete remission rate after induction chemotherapy and, with 402 days, a significantly shorter median overall survival (OS) (median OS for AML patients without AKI not reached). In this study, we demonstrate that the KIDGO classification allows mortality risk stratification for AML patients undergoing induction chemotherapy. Relatively mild AKI episodes have impact on the clinical course of these patients and can lead to chronic impairment of kidney function. Therefore, we recommend incorporating risk factors for AKI in decision-making considering nutrition, fluid management, as well as the choice of potentially nephrotoxic medication in order to decrease the incidence of AKI.

Among the diseases of the colon, diverticular disease occupies one of the leading positions, the frequency of which is currently 1.2 cases per 1000 people. Complications in this condition develop in 5% of cases and account for 3-5% of all patients with acute abdominal diseases. Surgical intervention is required in 15% to 30% of such patients. The mortality rate after surgical treatment of acute complications of the diverticular disease remains high, ranging from 7% to 25%. The purpose of our study was to compare the outcomes in the treatment of patients with acute destructive diverticulitis of the colon using traditional surgical treatment versus minimally invasive technologies. In the study, 114 patients diagnosed with acute destructive diverticulitis were examined. Group I consisted of 56 patients who underwent initial surgical interventions employing minimally invasive methods like laparoscopy, laparoscopic-assisted techniques, or percutaneous drainage guided by ultrasound. Group II comprised 58 patients who underwent the first surgical intervention through laparotomy access. The data of our study show that the overall proportion of patients with complications was higher in Group II – 20 (34.5%) compared to 6 (10.1%) in Group I (p=0.005). The application of diverse surgical methods did not notably impact the mortality rate, with 6 (10.3%) fatalities in Group II compared to 2 (3.6%) in Group I (p=0.2). Stoma creation was more frequent in Group II, in 40 (67%) patients, whereas in Group I, the occurrence of stomas was lower, in 15 (25.9%) cases. The average period to stoma closure was 5 months in Group II and 2 months in Group I. There was observed a decrease in the time of urgent surgery from 143±13.5 minutes in Group II to 65.7±15.2 minutes in Group I (p<0.01) and the duration of the first hospitalization from 14.2±1.8 days to 5.6±0.7 days, accordingly (p<0.01). When dealing with primary anastomosis or severe peritonitis, utilizing a laparoscope for dynamic laparoscopy allows for real-time monitoring of the abdominal cavity and early identification of complications, eliminating the need for scheduled laparostomy. The research data demonstrate that, while not affecting mortality, minimally invasive methods have several significant advantages, including a reduction in the number of complications, a decrease in the proportion of patients with stomas, a reduction in the time to reconstructive surgery, and a decrease in the duration of urgent surgery and the length of hospitalization.

The healthcare industry is one application for data envelopment analysis (DEA) that can have significant benefits for standardizing health service delivery. This narrative review focuses on the application of DEA in emergency departments (EDs) and the management of emergency conditions such as acute ischemic stroke and acute myocardial infarction (AMI). This includes benchmarking the proportion of patients that receive treatment for these emergency conditions. The most frequent primary areas of study motivating work in DEA, EDs and management of emergency conditions including acute management of stroke are sorted into five distinct clusters in this study: (1) using basic DEA models for efficiency analysis in EDs, i.e., applying variable return to scale (VRS), or constant return to scale (CRS) to ED operations; (2) combining advanced and basic DEA approaches in EDs, i.e., applying super-efficiency with basic DEA or advanced DEA approaches such as additive model (ADD) and slack-based measurement (SBM) to clarify the dynamic aspects of ED efficiency throughout the duration of a first-aid program for AMI or heart attack; (3) applying DEA time series models in EDs like the early use of thrombolysis and percutaneous coronary intervention (PCI) in AMI treatment, and endovascular thrombectomy (EVT) in acute ischemic stroke treatment, i.e., using window analysis and Malmquist productivity index (MPI) to benchmark the performance of EDs over time; (4) integrating other approaches with DEA in EDs, i.e., combining simulations, machine learning (ML), multi-criteria decision analysis (MCDM) by DEA to reduce patient waiting times, and futile transfers; and (5) applying various DEA models for the management of acute ischemic stroke, i.e., using DEA to increase the number of eligible acute ischemic stroke patients receiving EVT and other medical ischemic stroke treatment in the form of thrombolysis (alteplase and now Tenecteplase). We thoroughly assess the methodological basis of the papers, offering detailed explanations regarding the applied models, selected inputs and outputs, and all relevant methodologies. In conclusion, we explore several ways to enhance DEA’s status, transforming it from a mere technical application into a strong methodology that can be utilized by healthcare managers and decision-makers.

Migraine is a common and disabling primary headache disorder with a significant socioeconomic burden. The management of migraine is multifaceted and is generally dichotomized into acute and preventive strategies, with several treatment modalities. The aims of acute pharmacological treatment are to rapidly restore function with minimal recurrence, with the avoidance of side effects. The choice of pharmacological treatment is individualized, and is based on the consideration of the characteristics of the migraine attack, the patient's concomitant medical problems, and treatment preferences. Notwithstanding, a good understanding of the pharmacodynamic and pharmacokinetic properties of the various drug options is essential to guide therapy. The current approach and concepts relevant to the acute pharmacological treatment of migraine will be explored in this review.

Purpose To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. Methods The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation. Results 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO 2 /FiO 2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. Conclusions Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. Trial Registration: ClinicalTrials.gov NCT02010073.

Background: Lasmiditan, an oral 5-HT1F receptor agonist, has been recently approved for acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, scarce data is available regarding effectiveness and tolerability in the real-world setting. Objectives: To evaluate lasmiditan effectiveness and tolerability in the real-world setting in 16 Italian headache centers. Design: LasmiDitan as Acute migRaine Treatment (DART) study is a prospective, multicentric, observational study. Methods: We enrolled 58 participants with migraine (84.5% females, age 49.0 (45.2–52.9) years, 24.1% with chronic migraine) reporting 9.4 (7.4–11.3) monthly migraine days. Participants were instructed to treat their migraine attacks with oral lasmiditan 50 or 100 mg. Using an ad hoc electronic diary, participants prospectively collected migraine attack features at baseline and every 30 min after lasmiditan administration, up to 2 h post-dose. The primary outcome was 2-h pain freedom for the first-treated attack after lasmiditan intake. We also collected the occurrence of treatment-emergent adverse events (AE) after administration. Results: Overall, participants treated 100 attacks, of which 58 first-treated attacks. Regarding first-treated attacks, 44.8% of subjects rated migraine intensity as severe at lasmiditan intake. Pain freedom 2-h post-dosing was reported in 32.8% (19/58) of individuals and was associated with baseline pain intensity, being higher in subjects treating a mild/moderate attack (p = 0.044). Conversely, it was not influenced by timing of intake (p = 0.375), dosage (p = 0.727), or previous triptan failure (p = 0.351). Regarding all-treated attacks, pain freedom 2-h post-dosing was 37.0% (37/100). At least one AE was reported by 53.4% of participants (31/58), predominantly asthenia, dizziness, somnolence, anxiety or agitation, and paresthesia. Tolerability was rated as good-to-excellent by 51.8% of subjects. Conclusion: Our study supports clinical effectiveness of oral lasmiditan 50 and 100 mg for the treatment of acute migraine attacks. Lasmiditan effectiveness was not associated with the previous triptan failure and may therefore represent a valuable therapeutic option in subjects who did not benefit from, or have contraindications to, triptans. Trail registration: The study was preregistered on clinicaltrial.gov, NCT05903040 (https://clinicaltrials.gov/study/NCT05903040?cond=migraine&intr=lasmiditan&rank=5).

Background Rimegepant, a novel oral calcitonin gene-related peptide receptor antagonist, has been recently approved for the acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, no data is available regarding real-life effectiveness and tolerability. GAINER, a prospective, multicentric study, aimed to evaluate rimegepant effectiveness and tolerability in the real-world setting. Methods Our study involved 16 headache centers across Italy. The main outcomes were: i) 2 h pain freedom, and ii) occurrence of treatment-emergent adverse events after administration. Participants were instructed to treat one migraine attack with rimegepant 75 mg orally disintegrating tablet. Using an ad hoc diary, participants prospectively collected migraine attack features at baseline and every 30 min after rimegepant administration, up to 2 h post dose. A 24 h follow up was also collected. Results We enrolled 103 participants with migraine (74.8% female, mean age 44.4 [42.0 – 46.7] years, 24.3% with chronic migraine of whom 44.0% presented a concomitant diagnosis of medication overuse headache). The number of previously failed preventive classes was 2.7 [2.3 – 3.2]. Participants presented a mean of 9.6 [8.2 – 10.9] monthly migraine days at baseline. At rimegepant intake, 40.8% of patients rated migraine intensity as severe. Pain freedom 2 h post dose was reported in 44.7% (46/103) of individuals. Pain freedom 2 h post dose was not influenced by baseline pain severity ( p  = 0.316), but it was associated with timing of intake ( p  = 0.032) with a higher rate of 2 h pain freedom when rimegepant was taken within 1 h from pain onset. Mild adverse events were reported in 15.5% total attacks (16/103), predominantly fatigue ( n  = 6), gastrointestinal symptoms ( n  = 6), somnolence ( n  = 4), and transient cognitive difficulties ( n  = 3). Tolerability was rated as good-to-excellent in 85.4% cases (88/103). Conclusions Our data confirms rimegepant effectiveness and safety in the acute migraine treatment in a real-world setting in a cohort of participants that includes subjects with episodic or chronic migraine, medication overuse and a high number of prior preventive treatment failures. Trial registration The study was preregistered on clinicaltrial.gov, NCT05903027.