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As treatment options in advanced systematic lupus erythematosus (SLE) are limited, there is an urgent need for new and effective therapeutic alternatives for selected cases with severe disease. Bortezomib (BTZ) is a specific, reversible, inhibitor of the 20S subunit of the proteasome. Herein, we report clinical experience regarding efficacy and safety from all patients receiving BTZ as therapy for SLE in Sweden during the years 2014−2020. 8 females and 4 males were included with a mean disease duration at BTZ initiation of 8.8 years (range 0.7–20 years). Renal involvement was the main target for BTZ. Reduction of global disease activity was recorded by decreasing SLEDAI-2K scores over time and remained significantly reduced at the 6-month (p=0.007) and the 12-month (p=0.008) follow-up visits. From BTZ initiation, complement protein 3 (C3) levels increased significantly after the 2 nd treatment cycle (p=0.05), the 6-month (p=0.03) and the 12-month (p=0.04) follow-up visits. The urine albumin/creatinine ratio declined over time and reached significance at the 6-month (p=0.008) and the 12-month follow-up visits (p=0.004). Seroconversion of anti-dsDNA (27%), anti-C1q (50%) and anti-Sm (67%) was observed. 6 of 12 patients experienced at least one side-effect during follow-up, whereof the most common adverse events were infections. Safety parameters (C-reactive protein, blood cell counts) mainly remained stable over time. To conclude, we report favorable therapeutic effects of BTZ used in combination with corticosteroids in a majority of patients with severe SLE manifestations irresponsive to conventional immunosuppressive agents. Reduction of proteinuria was observed over time as well as seroconversion of some autoantibody specificities. In most patients, tolerance was acceptable but mild adverse events was not uncommon. Special attention should be paid to infections and hypogammaglobinemia.

Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the \"last resort\" choices of CRO infections. We explored the possible factors affecting PMB efficacy. This retrospective study involved CRO-infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had \"clinical success\" (CS) and \"clinical failure\" (CF). A total of 191 patients were enrolled: 110 in the CS group and 81 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700-1443.75) vs 800 (500-1112.5) mg; = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8-14) vs 8 (6-11) days; < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently. PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose, duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier: NCT00856544 and NCT00413699.

The definition of narcissism can be a moving target. Is it an excess of self-love? Profound insecurity? Low self-esteem? Too much self-esteem? Because of the multifaceted nature of narcissistic personality disorder (NPD), treating this disorder presents clinicians with a range of wholly unique challenges. Narcissism and Its Discontents recognizes the variable nature of NPD and provides a template for adjusting treatment to the patient rather than shoehorning the patient into a manualized treatment that may prove to be less effectual. This guide offers clinicians strategies, including transference and countertransference, to deal with the complex situations that often arise when treating narcissistic patients, among them, patient entitlement, disengagement, and envy. The authors provide a skillful integration of research and psychoanalytic theory while also addressing psychotherapeutic strategies that are less intensive but also useful -- being cognizant of the fact that a majority of patients do not have access to psychoanalysis proper. A chapter on the cultural aspects of narcissism addresses the recent societal fascination with NPD in the discourse on politics and celebrity, particularly in the age of social media. Regardless of the treatment setting -- psychoanalysis, psychotherapy, pharmacotherapy, partial hospital, or inpatient -- clinicians will find a wealth of approaches to treating a diverse and challenging patient population in Narcissism and Its Discontents.

A fascinating text that addresses the clinical and educational challenges of treating psychiatric patients from a truly multidisciplinary perspective using a case-based format, Approach to the Psychiatric Patient: Case-Based Essays is the only book of its kind and an indispensable addition to the mental health practitioner's library. The new edition builds upon the strengths that distinguished the first, with composite cases that are carefully constructed to capture real-world problems, followed by essays that provide clear and cogent perspectives on the case. These essays cover a wide range, from the more conventional (such as differential diagnosis of anxiety or the clinical characteristics of delirium) to the unusual and intriguing (such as creativity and mental illness or an analysis of the case in relation to the classic, Strange Case of Dr. Jekyll and Mr. Hyde). Every chapter has been revised, and the book boasts many new co-contributors, as well as the addition of completely new essays. For example, in the chapter on geriatric depression, several new essays have been added on the topics of collaborative care and the embedded psychiatrist, depression and medical illness, and biomarkers to identify depression subtypes, while the chapter on terminal illness features new essays on spirituality and meaning-centered therapy. In addition, there are new essays on co-occurring anxiety and alcohol use disorders, medication assisted treatment for stimulant use, treatment of body dysmorphic disorder, and more.The text possesses many useful attributes for the reader: • The more than 100 essays were written by a broad range of specialists, each with particular expertise in their aspect of the case, and the resulting commentary is focused and concise. • In addition to the case and discussions, each chapter offers an overview and summary points designed to facilitate further consideration of the patient and clinical situation and to focus on the key points.• The book's unique structure enhances its flexibility, allowing the reader to read a case and accompanying essays straight through, or to pick and choose as the need or whim arises.• The cases' clinical settings are diverse, ranging from inpatient hospitalizations and emergency room evaluations to outpatient assessments and long-term psychotherapies, maximizing relevance and resonance.• Each essay has its own bibliography, which provides both rigorous documentation and additional sources for more exploration of the topic. Approach to the Psychiatric Patient: Case-Based Essays distinguishes itself from prior texts in both the richness of its cases and the ingenuity of its format, and its multidisciplinary wisdom and insight will be appreciated by a wide range of readers.

OBJECTIVE： To evaluate the effectiveness and safety of the Xingnao Kaiqiao needling method for treating acute ischemic stroke.DATA SOURCES： We retrieved relevant randomized controlled trials involving Xingnao Kaiqiao acupuncture for treatment of acute ischemic stroke. The China National Knowledge Infrastructure, Weipu Information Resources System, Wanfang Medical Data System, Chinese Biomedical Literature Database, Cochrane Library, and Pub Med were searched from June 2006 to March 2016.DATA SELECTION： We analyzed randomized and semi-randomized clinical controlled trials that compared Xingnao Kaiqiao acupuncture with various control treatments, such as conventional drugs or other acupuncture therapies, for treatment of acute ischemic stroke. The quality of articles was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions（Version 5.1）, and the study was carried out using Cochrane system assessment methods. Rev Man 5.2 was used for the meta-analysis of the included studies.OUTCOME MEASURES： The mortality rate, disability rate, activities of daily living（Barthel Index）, and clinical efficacy were observed.RESULTS： Twelve studies met the inclusion criteria for this review. The meta-analysis showed that between Xingnao Kaiqiao acupuncture and the control treatment, Xingnao Kaiqiao acupuncture reduced the disability rate [risk ratio（RR） = 0.51, 95% confidence interval（CI） = 0.27-0.98, z = 2.03, P 〈 0.05], elevated the activities of daily living（weighted mean difference = 12.23, 95% CI： 3.66-20.08, z = 2.80, P 〈 0.005）, and had greater clinical efficacy（RR = 1.61, 95% CI： 1.23-2.09, z = 3.53, P 〈 0.0004）. However, there was no significant difference in mortality rate（RR = 0.61, 95% CI： 0.15-2.45, z = 0.70, P 〉 0.05）. CONCLUSION： The Xingnao Kaiqiao needling method is effective and safe for acute ischemic stroke. However, there was selective bias in this study, and the likelihood of measurement bias is high. Thus, more high-quality randomized controlled trials are needed to provide reliable evidence of the efficacy and safety of Xingnao Kaiqiao acupuncture in the treatment of acute ischemic stroke.

abstract Acetyl hexapeptide-3 has been used in anti-aging topical formulations aimed at improving skin appearance. However, few basic studies address its effects on epidermis and dermis, when vehiculated in topical formulations. Thus, the objective of this study was to determine the clinical efficacy of acetyl hexapeptide-3 using biophysical techniques. For this purpose, formulations with and without acetyl hexapeptide-3 were applied to the ventral forearm and the face area of forty female volunteers. Skin conditions were evaluated after 2 and 4-week long daily applications, by analyzing the stratum corneum water content and the skin mechanical properties, using three instruments, the Corneometer(r) CM 825, CutometerSEM 575 and ReviscometerRV600. All formulations tested increased the stratum corneum water content in the face region, which remained constant until the end of the study. In contrast, only formulations containing acetyl hexapeptide-3 exhibit a significant effect on mechanical properties, by decreasing the anisotropy of the face skin. No significant effects were observed in viscoelasticity parameters. In conclusion, the effects of acetyl hexapeptide-3 on the anisotropy of face skin characterize the compound as an effective ingredient for improving conditions of the cutaneous tissue, when used in anti-aging cosmetic formulations. resumo Acetil hexapeptídeo-3 tem sido utilizado como um ingrediente ativo em formulações tópicas antienvelhecimento para a melhoria da aparência cutânea. No entanto, poucos estudos avaliam seus efeitos na epiderme e derme, quando veiculado em formulações tópicas. Portanto, o objetivo desse estudo foi a determinação da eficácia clínica de acetil hexapeptídeo-3 utilizando técnicas de biofísica e de análise de imagem. Para tal, formulações contendo, ou não, acetil hexapeptídeo-3 foram aplicadas no antebraço volar e na face de voluntárias. As condições cutâneas foram avaliadas após duas e quatro semanas de aplicação diária das formulações, por meio da análise no conteúdo aquoso do estrato córneo e avaliação das propriedades mecânicas da pele, utilizando os equipamentos Corneometer(r) CM 825, CutometerSEM 575 e ReviscometerRV600. Todas as formulações avaliadas aumentaram o conteúdo aquoso do estrato córneo na face, o qual permaneceu constante até o fim do estudo. Por outro lado, somente as formulações contendo acetil hexapeptídeo-3 apresentaram efeito significativo nas propriedades mecânicas, por meio da diminuição da anisotropia da pele na face. Não foram observados efeitos significativos para os parâmetros de viscoelasticidade. Em conclusão, os efeitos de acetil hexapeptídeo-3 na pele caracteriza este peptídeo como um ingrediente ativo efetivo para a melhoria das condições cutâneas, quando utilizadas em formulações cosméticas.

The vertical infraclavicular block (VIB) of the brachial plexus is commonly used to provide local anesthesia (LA) of the upper limb. The original method involves LA injection at the mid-point of an infraclavicular line between acromion and jugular fossa. However, this method is ineffective in adult patients with variant anatomy. Two modified VIB methods have been previously suggested. This prospective observational, clinical study compared both modified VIB approaches. The study showed that modified VIB is easy, efficacious, and applicable to all adult patients; including those with small stature, extreme tallness, or variant anatomy.

While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF.