Background Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Previous studies have yielded inconsistent results. Objectives We sought to analyze long-term ...biologic survival and its associated variables in a large, real-life cohort of patients with moderate to severe chronic plaque psoriasis. Methods This was an observational retrospective study. Data were extracted from clinical records of 427 patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression. Results We analyzed 703 treatment courses. Overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months, 95% confidence interval 17.4-28.6) than in patients with body mass index less than 30 (37.3 months, 95% confidence interval 29.4-45.1, P = .001), and it was significantly higher for ustekinumab than for any other biologic agent (log rank test P < .001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment, and PASI75 and PASI90 responses at week 16 prolonged drug survival. Limitations Data were collected retrospectively. Conclusions These findings can facilitate the daily treatment of psoriatic patients and promote long-term effectiveness of biologic therapies.
IMPORTANCE: Infantile hemangiomas involute to some extent, but they often leave sequelae that may cause disfigurement. Factors determining the risk of permanent sequelae after regression are of ...crucial importance in treatment decision making. OBJECTIVES: To describe the sequelae left by infantile hemangiomas after natural involution and to identify clinical characteristics that could predict the most severe or a particular type of sequelae. DESIGN, SETTING, AND PARTICIPANTS: Multicentric retrospective cohort study of images from 187 infantile hemangiomas that had not received systemic treatment and had follow-up pictures until regression that were selected from photographic files taken between 2003 and 2013 at 4 university hospitals with large vascular clinics in 3 different countries. MAIN OUTCOMES AND MEASURES: Outcome measures were the type of sequelae classified as residual telangiectasia, anetodermal skin, redundant skin, persistent superficial component, and the degree of sequelae ranging from 1 to 4. RESULTS: A total of 184 hemangiomas were included. The overall incidence of significant sequelae was 101 of 184 (54.9%). The most common sequelae after involution were telangiectasias (145, 84.3%), fibrofatty tissue (81, 47.1%), and anetodermic skin (56, 32.6%). The average age at which hemangioma completed involution was 3.5 years. Superficial and deep hemangiomas left significantly fewer sequelae than combined hemangiomas (Mann-Whitney; superficial vs deep, OR, 1.6; 95% CI, 0.6-3.8; P = .81; superficial vs combined, OR, 3.3; 95% CI, 1.7-6.3; P < .001; deep vs combined, OR, 2.1; 95% CI, 0.9-5.1; P < .001). Hemangiomas with a step or abrupt border of the superficial component left more severe sequelae than those with a smooth border (χ2,OR, 3.4; 95% CI, 1.8-6.6; P < .001). Superficial hemangiomas with a cobblestone appearance or rough surface left more severe sequelae than those with a smooth surface (Kruskal-Wallis; α, 0.05; P < .001). Using multivariate analysis, combined hemangiomas with a superficial component and a step border were associated with more sequelae. CONCLUSIONS AND RELEVANCE: In this retrospective study of sequelae in a large cohort of untreated infants, we quantified the prevalence of permanent scarring and identified clinical features predictive of permanent sequelae. Our observations provide useful information at a time when the treatment paradigm for hemangiomas has changed. Such knowledge may help primary care physicians predict the risk of sequelae and identify high-risk lesions to implement early treatment.
Background
Laparoscopic sleeve gastrectomy (LSG) has increased in popularity in recent years as a definitive bariatric procedure. Despite its growing popularity worldwide, the surgical technique is ...not well standardized. There is a lack of evidence on the matter of the antrum size and its relation to gastric emptying and weight-loss outcomes. The aim of the study is to evaluate the influence of antrum size over gastric emptying and weight-loss outcomes.
Methods
Twenty-five patients were prospectively randomized according to the distance between the first firing and the pylorus: AR group (antrum resection—2 cm from the pylorus) and AP group (antrum preservation—5 cm from the pylorus). Gastric emptying (%GE) was evaluated by a gastric emptying scintigraphy before surgery, 2 months and 1 year after LSG. Antrum volume was measured using a MultiSlice CT Scan performed 2 months and 1 year after surgery. The percent of excess weight loss (%EWL) was calculated after 1 year follow-up.
Results
At 2 months after LSG the mean %GE was 69.7 ± 18 in the AR group and 72.8 ± 20 in the AP group (
p
= 0.69). At 1 year it was 66.5 ± 21 and 74.2 ± 16 in the AR and AP groups, respectively (
p
= 0.30). A significant accelerated gastric emptying was observed at 2 months (
p
= 0.025) and at 1 year (
p
= 0.013) in the AP group. Meanwhile in the AR group this increase was not significant (
p
= 0.12 at 2 months and
p
= 0.21 at 1 year). Differences regarding the %EWL between groups were no statistically significant (
p
= 0.74).
Conclusions
After LSG there is a global tendency to an accelerated gastric emptying, although only significant in the antrum preservation group; however, no differences were observed regarding the %EWL between groups after 1 year follow-up.
Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its ...role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective.
ClinicalTrials.gov NCT03173742.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In real-world scenarios, Janus Kinase (JAK) inhibitors are often offered to "difficult-to-treat" rheumatoid arthritis patients, quite different from those included in randomized controlled trials. ...Our study aimed to evaluate the influence of patient-related factors on the effectiveness and safety of JAK inhibitors in real-world clinical practice. This observational retrospective study involved rheumatoid arthritis patients who received treatment with either tofacitinib, baricitinib, upadacitinib, or filgotinib. At 12 months of treatment, reasons for and rates of JAK inhibitor treatment discontinuation were examined. Treatment retentions were analyzed through Cox proportional hazard regression models and Kaplan-Meier estimates. Patient-related factors that could influence treatment retention were evaluated for the discontinuation reasons of lack of effectiveness and adverse events. At 12 months of treatment, discontinuation rates for 189 JAK inhibitor treatments were: lack of effectiveness (24.3%), adverse events (20.6%), and other reasons (3.7%). The remaining 51.4% represents the treatment continuation rate. No patient-related factors evaluated had an influence on treatment discontinuation due to lack of effectiveness. Ae significantly increased the risk of treatment discontinuation due to adverse events (p = 0.030). In terms of age, at 12 month of treatment, discontinuation rates due to adverse events were: < 65 years, 14.4% vs. 65 years or older, 26.3% (p = 0.019). Rheumatoid arthritis patients aged 65 years or older showed an increased risk of JAK inhibitor treatment discontinuation due to adverse events. Factors not related to treatment discontinuation were: sex, rheumatoid arthritis disease duration, rheumatoid arthritis disease activity, seropositivity for rheumatoid factor, seropositivity for anti-cyclic citrullinated peptides, number of prior biologic treatments, number of prior JAK inhibitor treatments, concomitant use of glucocorticoids, and concomitant use of conventional synthetic disease-modifying antirheumatic drugs.
Falls are frequent among patients with debilitating disorders and can have a serious effect on health status. Mild cognitive disturbances associated with cirrhosis may increase the risk for falls. ...Identifying subjects at risk may allow the implementation of preventive measures. Our aim was to assess the predictive value of the Psychometric Hepatic Encephalopathy Score (PHES) in identifying patients likely to sustain falls. One hundred and twenty‐two outpatients with cirrhosis were assessed using the PHES and were followed at specified intervals. One third of them exhibited cognitive dysfunction (CD) according to the PHES (<−4). Seventeen of the forty‐two patients (40.4%) with CD had at least one fall during follow‐up. In comparison, only 5 of 80 (6.2%) without CD had falls (P < 0.001). Fractures occurred in 4 patients (9.5%) with CD, but in no patients without CD (P = 0.01). Patients with CD needed more healthcare (23.8% versus 2.5%; P < 0.001), more emergency room care (14.2% versus 2.5%; P = 0.02), and more hospitalization (9.5% versus 0%; P = 0.01) as a result of falls than patients without CD. Patients taking psychoactive treatment (n = 21) had a higher frequency of falls, and this was related to an abnormal PHES. In patients without psychoactive treatment (n = 101), the incidence of falls was 32.4% in patients with CD versus 7.5% in those without CD (P = 0.003). In the multivariate analysis, CD was the only independent predictive factor of falls (odds ratio, 10.2; 95% confidence interval, 3.4‐30.4; P < 0.001). The 1‐year probability of falling was 52.3% in patients with CD and 6.5% in those without (P < 0.001). Conclusion: An abnormal PHES identifies patients with cirrhosis who are at risk for falls. This psychometric test may be useful to promote awareness of falls and identify patients who may benefit from preventive strategies. (HEPATOLOGY 2012;55:1922–1930)
Background
Bariatric surgery in the older population has been the subject of ongoing debate but several studies have recently demonstrated its short-term advantages in this age group. It is not yet ...clear, however, whether these benefits are long-lasting.
Methods
We retrospectively analyzed patients with morbid obesity who underwent laparoscopy sleeve gastrectomy (LSG). These patients were divided into two groups: those above 60 years of age (older group) and those of 60 years or under (younger group). Variables evaluated included demographics and anthropometrics data, comorbidities, and daily medication requirements.
Results
Two hundred fifty-two patients underwent LSG, 57 in the older group and 195 in the younger group. Outcomes related to weight loss in the older subjects were modest compared to those in the younger population (older group %EWL 41.6 vs younger group %EWL 51.1,
p
< 0.05, older group %TWL 24.9% vs younger group %TWL 25.2%,
p
< 0.05). During follow-up, both older and younger patients showed an improvement in all the comorbidities: hypertension (older 82.5% vs 38.1%, younger 52.6% vs 29.2%,
p
< 0.05), type 2 diabetes mellitus (older 38.6% vs 27.3%, 34.9% vs 23.9%,
p
< 0.05), hyperlipidemia (older 75.4% vs 42.9%, younger 35.9% vs 21.1%,
p
< 0.05), and OSAHS (older 57.9% vs 30%, younger 40.4% vs 7.1%,
p
< 0.05). The average number of daily medications used to manage comorbidities decreased in both groups.
Conclusion
LSG in older patients is effective in terms of weight loss, improvement of comorbidities, and lower daily medication requirements up to 5 years of follow-up.
Graphical abstract
OBJECTIVEWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by ...evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.
METHODSPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.
RESULTSWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval CI 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).
CONCLUSIONPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.
CLINICALTRIALS.GOV IDENTIFIERNCT02238470.
Background:
Immune-related adverse events (irAEs) have been associated with improved efficacy in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1 blockade agents, while the ...concurrent use of corticosteroids seems to worsen it. We evaluated outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents in relation to the presence of irAEs and the reasons for using corticosteroids: whether for palliative cancer-related reasons or for the management of irAEs.
Methods:
Clinical outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents were calculated with regard to the presence of irAEs and the use of corticosteroids. A landmark analysis was performed to avoid immortal time bias due to the time-dependent nature of irAEs.
Results:
Out of a total of 267 patients, the 56.9% of patients who experienced irAEs had significantly improved outcomes. In the landmark analysis, median progression-free survival (PFS) was 12.4 months for patients with irAEs vs. 4.1 months for patients without irAEs (
p
< 0.001), while median overall survival (OS) was 28.2 vs. 12.5 months, respectively (
p
< 0.001). Likewise, objective response and disease control rates were significantly higher in patients experiencing irAEs: 48.6 vs. 22.8% and 77.1 vs. 39.6% (
p
< 0.001), respectively. Median OS was significantly shorter for patients receiving ≥10 mg of prednisone equivalent daily for cancer-related symptoms than for the rest of patients (<10 mg prednisone equivalent daily or for management of irAEs): 6 vs. 15.9 months (
p
< 0.001).
Conclusions:
IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.
Ventilation in the prone position for about 7 h/d in patients with acute respiratory distress syndrome (ARDS), acute lung injury, or acute respiratory failure does not decrease mortality. Whether it ...is beneficial to administer prone ventilation early, and for longer periods of time, is unknown.
We enrolled 136 patients within 48 h of tracheal intubation for severe ARDS, 60 randomized to supine and 76 to prone ventilation. Guidelines were established for ventilator settings and weaning. The prone group was targeted to receive continuous prone ventilation treatment for 20 h/d.
The intensive care unit mortality was 58% (35/60) in the patients ventilated supine and 43% (33/76) in the patients ventilated prone (p = 0.12). The latter had a higher simplified acute physiology score II at inclusion. Multivariate analysis showed that simplified acute physiology score II at inclusion (odds ratio OR, 1.07; p < 0.001), number of days elapsed between ARDS diagnosis and inclusion (OR, 2.83; p < 0.001), and randomization to supine position (OR, 2.53; p = 0.03) were independent risk factors for mortality. A total of 718 turning procedures were done, and prone position was applied for a mean of 17 h/d for a mean of 10 d. A total of 28 complications were reported, and most were rapidly reversible.
Prone ventilation is feasible and safe, and may reduce mortality in patients with severe ARDS when it is initiated early and applied for most of the day.
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