Therapy For Relief Of Symptoms Research Articles

Bee Sting-induced Nephrotic Syndrome in a Child: A Case Report with Review of Literature

Abstract Background: Nephrotic syndrome (NS) is common in children, and it is usually idiopathic. Bee sting-induced NS in children is rarely reported. Clinical Description: A 9-year-old female child presented with a complaint of generalized edema for 2 days which started to develop 4 days after being stung on the dorsum of her right foot by a bee. She had pedal edema, facial puffiness, and abdominal distension. Management and Outcome: Laboratory investigations showed proteinuria, low serum protein, elevated serum cholesterol, serum triglycerides, and immunoglobulin E levels. A diagnosis of NS secondary to bee sting was made. The patient was treated with supportive measures for edema. There was a significant clinical and biochemical improvement by 10 days. Conclusion: This case reiterates the association between allergen exposure and NS, which is hardly reported in children. Such a phenomenon may be transient with requirement of only supportive therapy for symptom relief.

Impact of ovarian vein embolization in recurrent varicose veins of the lower extremity.

Background: The treatment success of catheter-based ovarian vein embolization due to peripheral varicose veins and ovarian vein reflux (OVR) should be investigated in this clinical investagtion. Patients and methods: For this study, 95 female patients were identified over a 5-year period (beginning of 2006 to end of 2011) after catheter-based coil (+/- chemical) embolization of the ovarian vein due to peripheral primary or recurrent varicose veins and proven reflux in the ovarian vein. Treatment success was retrospectively assessed in 2014 by means of a structured telephone interview (n=60), clinical examination (n=56), duplex ultrasound (n=56) and magnetic resonance imaging (n=51) in patients who were willing to participate in the study. Results: After an average of 51.9 months, 95.2% of the 60 included patients were diagnosed with recurrent varicose veins by duplex sonography and 88.1% by clinical examination. In 15.2%, a new intervention was required due to clinical symptoms. The median recurrence-free time was 47.0±5.5 months. A significant improvement by therapy was reported for all subjective symptoms in both pelvis and legs. No significant correlation between radiological findings and complaints or between radiological findings and clinical recurrence was found. Conclusions: The medical history of female patients with peripheral varicose veins should obligatorily include the question of symptoms in the pelvis. An appropriate diagnostic should follow in order to prevent a possible overlook of a pelvic leak point. Only then an individually adapted therapy for symptom relief is possible. Catheter-based ovarian vein embolization is one optional safe procedure that leads to significant improvement of subjective symptoms but does not necessarily prevent recurrent varicose veins.

COVID-19-related delays of botulinum toxin injections have a negative impact on the quality of life of patients with dystonia and spasticity: a single-center ambulatory care study

BackgroundBotulinum toxin A (BoNT-A) is considered a safe and effective treatment for spasticity and dystonia. Individual interinjection intervals are critical for the maintenance of the effect. In Austria, BoNT outpatient clinics were shutdown from November to December 2020 during COVID-19 control measures, leading to rescheduling of BoNT-A injections. This survey aimed at investigating the influence of injection delays on symptoms, physical functioning, and quality of life (QoL) of the affected patients.MethodsBetween April and July 2021, 32 outpatients (21 females, mean age: 63.4 ± 12.1 years) treated ≥ 12 months at the BoNT outpatient clinic Horn-Allentsteig (Austria) and experienced ≥ 2 week injection delays, completed a structured face-to-face questionnaire.ResultsIndications were dystonia (34%), spasticity (63%), and hyperhidrosis (3%). Injections were delayed by 10 weeks (median, range: 2–15). Muscle cramps increased in 95% of patients with spasticity, muscle twitches in 91% of those with dystonia, and pain in 9% and 60% for dystonia and spasticity, respectively. Overall, 75% reported functional worsening, and deterioration in QoL by 62.6% ± 16.8 (mean ± SD). The impact on QoL correlated with the subjective global improvement induced by BoNT-A (Rs: 0.625; p < 0.001). For 75%, long-term assurance of BoNT-A therapy was very important, and 81% felt their patient rights not respected.ConclusionsCOVID-19-related delays in BoNT-A injections illustrate the importance of this therapy for symptom relief, functional outcome, and QoL in patients suffering from involuntary muscle hyperactivity. BoNT-A therapy is essential and has to be guaranteed even in circumstances such as the COVID-19 pandemic.

361 Identification of a new molecular modulator of severity in recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare disorder characterized by cutaneous fragility of the skin and mucous, due to COL7A1 mutations. Patients with RDEB have a poor quality of life as result of chronic wounds that trigger fibrotic processes and facilitate the development of highly aggressive squamous cell carcinomas. To find new disease-severity modulators, we previously reported a transcriptomic study (RNA-Seq) in two RDEB siblings with marked phenotypic differences despite being genotypically identical for COL7A1 (c.6527insC/c.6527insC). Enrichment analysis of the differentially expressed genes suggested differences regarding the extracellular matrix (ECM), cell contraction, and response to TGF-β, among others. Here, we explored in detail the biological relevance of some of these differentially altered processes. In particular, fibroblasts from the less affected sibling (M-RDEB) showed reduced response to TGF-β stimulus and lower contractile capacity of collagen lattices, contrary to what was observed in other RDEB patients (including the sister with severe phenotype) and similar to the behavior of fibroblasts from healthy donors. Interestingly, M-RDEB fibroblasts upregulate a previously undisclosed ECM protein capable of inhibiting the TGF-β pathway, and presumably responsible -at least in part- for the mild phenotype observed in M-RDEB. Overexpression of the gene encoding this factor in fibroblasts from the sister with severe phenotype (S-RDEB) counteracted TGF-β response and cell contraction capacity in in vitro functional assays. A similar result was obtained when treating S-RDEB fibroblasts with the molecule as a recombinant protein. Thus, our study identified new modulators and druggable targets in RDEB pathophysiology, which would enable novel symptom relief therapies to tackle disease progression.

Case Series of Metastatic VIPoma With Partial Response to Somatostatin Receptor Ligand and Review of Therapeutic Options

Background: Vasoactive intestinal polypeptide secreting islet cell tumors (VIPoma) are rare neuroendocrine tumors of pancreatic origin, characterized by secretory diarrhoea and electrolyte imbalances. Metastasis, commonly hepatic, frequently occur at diagnosis in up to 80% patients. Surgery of the primary tumour remains the gold standard management and in metastatic tumors, somatostatin receptor ligands (SRL) are the drugs of choice for symptom relief and disease control. Some patients will require other approaches to control symptoms, such as liver-targeted therapy, peptide receptor radionuclide therapy (PRRT) or chemotherapy. We describe a case series of metastatic VIPoma which partially-responded to SRL and review of other treatment modalities to achieve disease and symptom control. Case: We report 3 cases, ages 37 to 58 years, with metastatic VIPoma whom presented with secretory diarrhoea, hypokalaemia, achlorhydria and elevated serum VIP levels. CT and 68Gallium PET-CT imaging identified metastases in liver, bone, lungs, spleen and lymph nodes. One case underwent distal pancreatectomy and splenectomy at diagnosis and two cases were advanced and non-resectable. All received long-acting SRL initially and achieved partial control of the gastrointestinal symptoms. Two cases underwent Peptide Receptor Radionuclide Therapy (PRRT) and one case received cytotoxic chemotherapy. Two patients have progressive disease and one succumbed to advanced disease. For inoperable disease, PRRT is useful adjuvant therapy for symptom relief and may improve progression free survival (PFS). Cytotoxic chemotherapy is an option for patients with progressive or symptomatic unresectable tumor. Chemoembolization or liver-targeted therapy are used in liver metastasis for loco-regional control. Alfa-interferon and targeted therapies such as everolimus and sunitinib are other treatment options that can be considered. Conclusion: Metastatic VIPoma remains a challenging disease to manage, requiring multimodal treatment approaches. With timely diagnosis and advancing therapeutic options, more patients can achieve improved symptom and disease control as well as increased survival.

Safety and tolerability of nabiximols oromucosal spray: a review of real-world experience in observational studies, registries, and case reports

ABSTRACT Introduction : Nabiximols oromucosal spray,a cannabis-based medicine containing a balanced ratio of Δ-9-tetrahydrocannabinol and cannabidiol, is approved widely as an add-on therapy for symptomatic relief of spasticity in people with multiple sclerosis (MS). Most safety data for nabiximols derive from use in MS spasticity, with some data available from the analgesia area. Areas covered : This review compiles safety and tolerability data from all published observational studies, registry analyses, and case reports identified in systematic searches in which nabiximols oromucosal spray was investigated for spasticity (n = 20) and/or chronic non-cancer pain (n = 4). Aligning with the known safety profile of nabiximols as demonstrated in randomized controlled trials, common adverse events reported consistently across studies conducted under clinical practice conditions were dizziness, fatigue and somnolence. The serious adverse event (SAE) rate with nabiximols in MS spasticityobservational studies was 3.1% (137/4351). A total of 39 treatment-related SAEs were reported in 32 patients with spasticity, all of which (where specified) were resolved. No treatment-related SAEs were recorded in nabiximols pain studies. Expert opinion : Real-world experience with nabiximols oromucosal spray in treating spasticity and chronic pain indicates that, overall, it is well tolerated and has a good safety profile.

Impactos do tratamento hormonal e não hormonal sobre a sintomatologia vasomotora de mulheres climatéricas

O artigo busca analisar os diferentes tratamentos hormonais e alternativos, que visam atenuar as ocorrências vasomotoras e sua relação com a melhora na qualidade de vida das mulheres climatéricas. O climatério é definido como o período de transição entre a fase reprodutiva e não reprodutiva da mulher, marcado pela diminuição da secreção de estrogênio. Os desequilíbrios hormonais que ocorrem durante esse período, são responsáveis pelas manifestações que prejudicam a qualidade de vida da mulher, como os sintomas vasomotores, dentre eles fogachos e sudorese, sendo estes os fenômenos mais comuns no diagnóstico do climatério. Nesse período de transição, cerca de 25% das mulheres irão necessitar de terapia para o alívio dos sintomas. O tratamento durante essa fase deverá ser individualizado para cada caso específico, avaliando sempre as características apresentadas por cada paciente, e pode variar entre Terapia de Reposição Hormonal (TRH), não hormonal e tratamento não farmacológico. A TRH utilizada para o controle dos fenômenos climatéricos possui variação de resultados, conforme o esquema de utilização das drogas, e não é aconselhado o uso prolongado, devido ao aparecimento de reações adversas, como a trombose venosa.

Predictors and Long Term Outcomes for DLBCL Patients Undergoing Surgery Prior to Systemic Therapy

Background Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 22% of newly diagnosed non-Hodgkin's lymphoma per year in the United States. Combination chemoimmunotherapy with or without radiation therapy is recommended for the upfront treatment of DLBCL (Yang Liu, AJH,2019). A minority of patients undergo surgery prior to the initiation of systemic therapy for symptom relief or treatment of complications related to the disease. There are concerns on the delay in initiation of systemic therapy when surgery is performed and the potential impact on long term survival in this aggressive chemosensitive disease. We aimed to explore the characteristics of patients undergoing surgery prior to systemic therapy (sxfirst), the predictors for sxfirst and the survival outcomes. Methods We queried the National Cancer Database for patients with DLBCL (ICD-0-3 code 9680) diagnosed from 2006-2015. Inclusion criteria were patients that received systemic therapy as first-line course of treatment and excluded patients with incomplete or missing data for disease stage, treatment characteristics and follow-up. We also excluded patients who underwent biopsy procedures for diagnosis and local procedures such as tumor destruction or ablation. Subgroup analysis of patients that received sxfirst was performed. Time-to-initial therapy (TTI) was defined as time in days (d) from diagnosis to systemic therapy. Survival was measured in terms of months (m) from the day of diagnosis. Stepwise multivariate logistic regression analysis for predictors of sxfirst and propensity score adjusted survival analysis was performed. Results Of 208,748 patients with DLBCL, 138,096 patients met the inclusion criteria of whom 6,381 (4.6%) were sxfirst. The characteristics of sxfirst are summarized in Table 1. Median age was 66 (interquartile range IQR 55-75) years and 61.1% were males. Majority were non-Hispanic whites, had private or medicare insurance, had comorbidity score of 0 and stage I disease. Most patients were treated in comprehensive community cancer centers. The top 5 extra-nodal disease sites were gastrointestinal (26.2%), male reproductive system (16.4%), brain and spinal cord (6.4%), endocrine system (4.1%) and head and neck (3.0%). The median follow up was 47.6 (IQR 14.0-78.9) months. The predictors for sxfirst are described in Table 2. The following disease sites were associated with higher likelihood of sxfirst: male reproductive system (p-value&amp;lt;0.005), gastrointestinal system (p-value&amp;lt;0.005), endocrine system (p-value&amp;lt;0.005), brain and spinal cord (p-value=0.01) and head and neck (p-value=0.02) while the following factors were associated with lower likelihood of sxfirst - medicaid insurance (p-value=0.01), comorbidity score &amp;gt;=3 (p-value 0.007), more recent year of diagnosis, advanced stages of disease and presence of B-symptoms. The TTI for systemic therapy was delayed in sxfirst group - 34 (IQR 22-51) days vs. 21 (IQR 11-35) days, p-value&amp;lt;0.005. The 5-year overall survival for the sxfirst group was 64% (95% CI 62-65%) vs. 57% (95% CI 56-57%)- HR 0.75 (95% CI 0.71 - 0.81). The factors associated with increased mortality were advanced age, higher comorbidity score, lower educational status, advanced clinical stage of the disease, presence of B-symptoms , disease primarily located in the bone, brain and spinal cord. Conclusion The findings of the present study are twofold. First, the present study describes the characteristics and predictors of sxfirst among DLBCL patients. Second, if surgery is absolutely necessary prior to systemically treating DLBCL, the study suggests that the delay does not seem to impact long term survival of these patients and is similar to the 5-year overall survival (64%) reported for DLBCL when all stages and treatment strategies are combined (seer.cancer.gov/statfacts/dlbcl). While there are unmeasured confounding factors as a result of the absence of adequate prognostic markers and treatment characteristics in the database, it is possible that surgery truly doesn't impact the survival outcomes significantly. Further evaluation of this practical question is warranted in large scale prospective studies. Disclosures Khan: Abbvie: Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Beigene: Honoraria; Seattle Genetics: Honoraria. Fazal:Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Skin Fragility: Perspectives on Evidence-based Therapies.

The term skin fragility disorders describes a group of conditions in which the structural integrity of the skin is compromised and its resistance to external shear forces diminished. Skin fragility can have different causes, ranging from genetic variations to inflammatory or physical phenomena. The genetic skin fragility disorders, collectively called epidermolysis bullosa, serve as a paradigm for the study of causes and mechanisms of skin fragility. Recent biomedical research has revealed substantial genetic heterogeneity of the epidermolysis bullosa group, delivered ample new knowledge on its pathophysiology, and facilitated the design of evidence-based therapeutic strategies. The therapy development process extends from in vitro testing to preclinical validation in animal models, and clinical trials. This article reviews different approaches to curative and symptom-relief therapies, and appraises their status and perspectives for clinical implementation.

A pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy (CIPN).

111 Background: Short- and long-term toxicity of platinum compounds and taxanes includes development of CIPN. With an increased interest regarding the role of complementary approaches for symptom control, we investigated massage therapy for symptomatic relief of chronic CIPN. Methods: This pilot study evaluated the optimum treatment schedule and initial efficacy of a standardized Swedish massage technique to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, no other history of attributable causes; self-reported neuropathy score ≥3, 0-10 scale; ≥ 6 months since last chemotherapy treatment; age ≥ 18. Patients (pts) were randomized to one of four groups: 1) LE massage 3 times (3X) week for 4 weeks; LE massage 2X week for 6 weeks; 3) head/neck/shoulder (control) massage 3X week for 4 weeks; or 4) control massage 2X week for 6 weeks. Massage completion rate was examined and symptoms of CIPN measured with the Pain Quality Assessment Scale [PQAS (Range: 0-10); subscales of SP (surface pain), DP (deep pain), and PP (paroxysmal pain)] at baseline and at 10 weeks. Results: 71 pts fulfilled inclusion criteria: 77.5% women; 57.7% (breast cancer), and 42.3% (GI cancer); mean age 60.3 y/o (range: 40-77). Average length of time since the end of chemotherapy was &gt; 3 yrs. Mean massage completion rates (max = 12) were 8.9 (SD 4.2) for 3X week and 9.8 (4.0) for 2X week with no statistical differences. There were no statistically significant differences in PQAS scores at follow-up between site-specific massage groups (lower extremity vs controls). Pts who had massage 3X week reported statistically and clinically significantly improved PQAS scores versus those who had massage 2X week (change scores: PQAS-SP: -2.3 vs. -0.6, p = 0.001; PQAS-DP: -2.1 vs. -0.9, p = 0.008; PQAS-PP: -2.3 vs. -1.0, p = 0.025), with sustained improvement in the 3X week group, but minimal change in the 2X week group. Conclusions: We observed sustained reduction in pts with long-term CIPN up to 6 weeks after treatment completion for the more intensive 3X week massage group, regardless of treatment site. A large-scale efficacy trial is warranted to validate the role of oncology massage therapy for CIPN. Clinical trial information: NCT02221700.

Clinical Roundup: Selected Treatment Options for Multiple Sclerosis—Part 2

Alternative and Complementary TherapiesVol. 25, No. 5 Free AccessClinical Roundup: Selected Treatment Options for Multiple Sclerosis—Part 2Published Online:8 Oct 2019https://doi.org/10.1089/act.2019.29236.cruAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Massage TherapyResearch reveals that many people with multiple sclerosis (MS) turn to massage therapy for symptom relief. In fact, massage therapy is among the most common complementary and alternative medicine (CAM) therapies that people with MS utilize.1 Fatigue, pain, spasticity, and impaired gait, balance, and motor function are among the symptoms that patients are seeking to relieve when turning to CAM therapies such as massage.In a randomized controlled trial, Negahban and colleagues2 explored the effects of massage therapy on people with a variety of MS symptoms. In this study, a small group of people with MS were randomly assigned to massage only, exercise only, a combination of massage and exercise therapy, or a control group (standard care). Participants in the therapeutic interventions groups received fifteen 30-minute sessions over the course of 5 weeks. Results showed that participants in the massage therapy and exercise therapy groups experienced decreased fatigue and spasticity and also improved balance, walking endurance, and quality of life (QOL). Compared with the exercise alone group, participants in the massage therapy alone group and massage–exercise group experienced greater improvement in pain reduction. All intervention groups showed improvements over the control group.Another small study by Backus and colleagues3 found that people with MS who received a one-hour once weekly massage therapy session for six weeks experienced improvements in fatigue, pain, health perception, and QOL compared with before the intervention. The study authors commented: “These findings are meaningful given the prevalence of fatigue and pain in people with MS, and the extent to which these symptoms impact an individual's perception of health and quality of life.”3There is limited research on the effects of massage therapy on symptoms in people with MS, and further research is needed. However, findings such as those presented here suggest that massage therapy may be a beneficial CAM option, which is helpful in light of the fact that many people with MS already seek out massage therapy. Importantly, studies such as those mentioned help clinicians target their CAM therapy recommendations for specific symptoms in a unique population of patients such as people with MS.

Newer Treatment Modalities in Epidermolysis Bullosa.

The term epidermolysis bullosa (EB) refers to a group of hereditary skin blistering diseases. The group is clinically and genetically heterogeneous, but all EB forms are associated with mechanically induced skin blistering and fragility. The causative gene mutations of most EB types are known. The current international consensus classification contains four main types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS). The classification is based on the morphological level of blister formation. In EBS, the split is intra-epidermal, in JEB along the basement membrane and in DEB below the basement membrane. In Kindler syndrome, the dermal-epidermal junction is disorganized, and blisters can occur on all three levels. Each major EB type has further subtypes which may differ in terms of their genetic, biological or clinical characteristics. Traditionally, EB treatments have been symptomatic, but increasing understanding of disease etio-pathogenesis is facilitating development of novel evidence-based therapy approaches. First gene- and cell-based therapies are being tested at preclinical level and in clinical trials. New knowledge on secondary disease mechanisms has led to development and clinical testing of urgently needed symptom-relief therapies using small molecules and biologicals.

ROCK, PAPER, SCISSORS, ASTHMA, BRONCH: ROCK BEATS ASTHMA

Introduction Broncholithiasis occurs due to calcified substance found in the bronchial tree. Patients present with wheezing, cough, shortness of breath, and less commonly lithoptysis. Broncholiths can result in recurrent post obstructive pneumonia and bronchiectasis. In symptomatic patients, rigid or flexible bronchoscopy is often needed. We present a case of broncholithiasis and treatment with bronchoscope removal. Case Description A 52-year-old female non-smoker was evaluated for a three-year history of non-productive cough, globus sensation, shortness of breath, wheezing, fatigue, halitosis, and weight loss. She had a history of two episodes of chest x-ray proven pneumonia. Physical examination revealed expiratory wheezing. A sinus CT scan was normal. Patient had a positive methacholine challenge test. However, the patient did not respond to high dose inhaled corticosteroid/long-acting beta-agonist inhalers or systemic steroids for asthma. As this was an atypical presentation for asthma and the patient did not respond to standard therapy, further testing was performed. After CT of the chest showed a broncholith in a right sided bronchus, flexible bronchoscopy was utilized to remove the broncholith (Fig. 1). She subsequently felt immediate relief and the symptoms subsided. After the procedure, patient recalled possible lithoptysis a few months earlier. Discussion This case demonstrates the importance of further investigation even with a positive methacholine challenge test in a patient with recurrent pneumonia where patient symptoms do not clearly fit the clinical picture of asthma. Recognition of this process is critical in symptomatic patients for bronchoscope therapy for symptom relief.

Burden, Prevalence, and Treatment of Uterine Fibroids: A Survey of U.S. Women.

Most women will experience uterine fibroids by the age of 50, yet few data exist describing the overall patient experience with fibroids. The objective of this population-based survey was to characterize symptom burden, patient awareness, and treatment decision-making for fibroids, including a comparison among women of varying backgrounds. Women (≥18 years) were recruited via email from GfK KnowledgePanel®, a representative panel of US households, or identified with opt-in consumer panels. The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QOL) questionnaire and Aberdeen Menorrhagia Severity Scale (AMSS) were included. Eligible women were grouped into three cohorts: "at-risk" (symptoms suggestive of fibroids without clinical diagnosis, n = 300), "diagnosed" (n = 871), and fibroid-related "hysterectomy" (n = 272). Cohort and intracohort race/ethnicity and income analyses revealed differences in symptom burden, awareness/perception, and treatment history. Based on UFS-QOL scores, at-risk women reported significantly greater symptom severity and decreased health-related QOL versus diagnosed women; Hispanic women reported greater symptom severity versus white and black women. At-risk women also reported heavy menstrual bleeding and significant impact on work productivity. Among diagnosed women, 71% used pharmacologic therapy for symptom relief, and 30% underwent surgical or procedural treatment. Initial discussions with healthcare providers significantly impacted treatment outcomes; the hysterectomy cohort was most likely to first discuss hysterectomy. Women with fibroids or symptoms suggestive of fibroids experience significant distress that reduces QOL, particularly racial minorities and women in lower income brackets. Survey results suggest that many women are likely undiagnosed, underscoring the need for improved awareness and education.

Recent advances in understanding and managing epidermolysis bullosa.

Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous skin fragility disorder characterized by trauma-induced skin dissociation and the development of painful wounds. So far, mutations in 20 genes have been described as being associated with more than 30 clinical EB subtypes. The era of whole-exome sequencing has revolutionized EB diagnostics with gene panels being developed in several EB centers and allowing quicker diagnosis and prognostication. With the advances of gene editing, more focus has been placed on gene editing-based therapies for targeted treatment. However, their implementation in daily care will still take time. Thus, a significant focus is currently being placed on achieving a better understanding of the pathogenetic mechanisms of each subtype and using this knowledge for the design of symptom-relief therapies, i.e. treatment options aimed at ameliorating and not curing the disease.

Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study.

Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to (1) identify patient-prioritized symptoms for the development of symptom relief therapies and (2) elicit preferences for treatments among individuals receiving hemodialysis. We conducted a mixed methods study that included focus groups in Carrboro, North Carolina; Tucson, Arizona; and Seattle, Washington and a nationally distributed online survey. Focus group transcripts were analyzed for patterns, and the highest priority symptoms were determined on the basis of frequency and report severity. We used focus group findings to inform survey items. Focus group and survey results were crossvalidated and synthesized for final symptom prioritization. There were 32 participants across three focus groups and 87 survey respondents from 27 states in the United States. The physical symptoms of insomnia, fatigue, muscle cramping, and nausea/vomiting and the mood symptoms of anxiety and depressed mood were reported by participants in all focus groups. Among survey respondents, fatigue (94%), cramping (79%), and body aches (76%) were the most common physical symptoms, and feeling depressed (66%), worried (64%), and frustrated (63%) were the most common mood symptoms. The top-prioritized symptoms were consistent across focus group and survey participants and included the physical symptoms insomnia, fatigue, and cramping and the mood symptoms anxiety, depression, and frustration. Participants indicated that symptom frequency, duration, unpredictability, and social and financial effects factored most heavily into symptom prioritization. Patients prioritized the physical symptoms of insomnia, fatigue, and cramping and the mood symptoms of anxiety, depression, and frustration as the top symptoms for which to find new therapies.

Возможности гидролизата плаценты человека в комплексном лечении симптомов генитоуринарного синдрома в постменопаузе

Article is devoted an actual problem of modern gynecology - correction of the symptoms genitourinary syndrome (GUS), which has important medical and social importance. In addition to traditional hormone therapy, modern medicine has a broad range of metabolic substances, antioxidants and reparants to treat women with clinical manifestations of GUS. In this prospective study were 62 women aged up to 60 years in postmenopausal women with clinical symptoms of GUS, for the comprehensive treatment which the metabolic therapy was used the Melsmon (human placenta extract for subcutaneous injection).The results of the study demonstrated high clinical efficiency of the use of this therapy for relief of symptoms of GUS that improve the quality of life for women of postmenopausal age.

Primary Prevention of Sudden Cardiac Death in Patients with Heart Failure: How Effective is Current Pharmacologic Therapy?

Sudden cardiac death is the most common cause of death in the early stages of heart failure. Implantable cardioverter-defibrillator therapies substantially reduce sudden cardiac death but incur morbidity and are expensive, so are recommended only after failure of optimal medical therapy. Guidelines recommend simultaneous first-line therapy with an angiotensin converting enzyme inhibitor and a beta blocker for heart failure with reduced ejection fraction, with diuretic therapy for symptom relief. The all-cause mortality benefit of angiotensin converting enzyme inhibitors (or angiotensin receptor blockers) in this setting is largely attributable to reduced deaths related to disease progression. Addition of a beta blocker improves both all-cause survival and rates of sudden cardiac death. Where symptoms persist, introduction of a mineralocorticoid receptor antagonist is recommended and can reduce sudden cardiac death. If symptoms continue, substitution of the angiotensin converting enzyme inhibitor with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan significantly reduces all-cause mortality, with the benefit arising from fewer deaths from both sudden cardiac death and worsening heart failure. Further medical interventions should be instituted in specific situations as required. Disappointingly, despite evidence-led guidelines, approximately a quarter of patients who have heart failure with reduced ejection fraction do not receive standard therapy with an angiotensin converting enzyme inhibitor and beta blocker. It remains to be seen if recent guidelines for successive interventions in the event of non-response to standard therapy are more effectively adopted.

The in vivo efficacy and side effect pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long-acting β 2-adrenoceptor agonist in preclinical animal species.

Bronchodilators are a central therapy for symptom relief in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, with inhaled β2-adrenoceptor agonists and anticholinergics being the primary treatments available. The present studies evaluated the in vivo pharmacology of (R)-6-[[3-[[4-[5-[[2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pent-1-ynyl]phenyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide (GS-5759), a novel bifunctional compound with both phosphodiesterase 4 (PDE4) inhibitor and long-acting β2-adrenoceptor agonist (LABA) activity, which has been optimized for inhalation delivery. GS-5759 dose-dependently inhibited pulmonary neutrophilia in a lipopolysaccharide (LPS) aerosol challenge model of inflammation in rats with an ED50 ≤ 10 μg/kg. GS-5759 was also a potent bronchodilator with an ED50 of 0.09 μg/kg in guinea pigs and 3.4 μg/kg in dogs after methylcholine (MCh) and ragweed challenges respectively. In cynomolgus monkeys, GS-5759 was dosed as a fine-particle dry powder and was efficacious in the same dose range in both MCh and LPS challenge models, with an ED50 = 70 μg/kg for bronchodilation and ED50 = 4.9 μg/kg for inhibition of LPS-induced pulmonary neutrophilia. In models to determine therapeutic index (T.I.), efficacy for bronchodilation was evaluated against increased heart rate and GS-5759 had a T.I. of 700 in guinea pigs and >31 in dogs. In a ferret model of emesis, no emesis was seen at doses several orders of magnitude greater than the ED50 observed in the rat LPS inflammation model. GS-5759 is a bifunctional molecule developed for the treatment of COPD, which has both bronchodilator and anti-inflammatory activity and has the potential for combination as a triple therapy with a second compound, within a single inhalation device.

Prescription Pattern of Chinese Herbal Products for Diabetes Mellitus in Taiwan: A Population-Based Study

Background. Traditional Chinese medicine (TCM), when given as a therapy for symptom relief, has gained widespread popularity among diabetic patients. The aim of this study is to analyze the utilization of TCM among type 2 diabetic patients in Taiwan. Methods. The use of TCM for type 2 diabetic patients were evaluated using a randomly sampled cohort of 1,000,000 beneficiaries recruited from the National Health Insurance Research Database. Results. Overall, 77.9% (n = 31,289) of type 2 diabetic patients utilized TCM and 13.9% (n = 4,351) of them used TCM for the treatment of type 2 diabetes. Among the top ten most frequently prescribed herbal formulae, four remedies, Zhi-Bo-Di-Huang-Wan, Qi-Ju-Di-Huang-Wan, Ji-Sheng-Shen-Qi-Wan and Ba-Wei-Di-Huang-Wan are derivative formulae of Liu-Wei-Di-Huang-Wan. In other words, Liu-Wei-Di-Huang-Wan and its derivatives were found to be the most common herbal formulae prescribed by TCM doctors for the treatment of diabetes in Taiwan. Conclusion. Although some evidence does support the use TCM to treat diabetes, the results from the current study may have been confounded by placebo effect, which emphasize the need for well conducted, double-blind, randomized, placebo-controlled studies in order to further evaluate the efficacy of Liu-Wei-Di-Huang-Wan on patients with type 2 diabetes.