Symptoms and medications change patterns for Parkinson's disease patients stratification

Quality of life of patients with Parkinson's disease degrades significantly with disease progression. This paper presents a step towards personalized management of Parkinson's disease patients, based on discovering groups of similar patients. Similarity is based on patients’ medical conditions and changes in the prescribed therapy when the medical conditions change. We present two novel approaches. The first algorithm discovers symptoms’ impact on Parkinson's disease progression. Experiments on the Parkinson Progression Markers Initiative (PPMI) data reveal a subset of symptoms influencing disease progression which are already established in Parkinson's disease literature, as well as symptoms that are considered only recently as possible indicators of disease progression by clinicians. The second novelty is a methodology for detecting patterns of medications dosage changes based on the patient status. The methodology combines multitask learning using predictive clustering trees and short time series analysis to better understand when a change in medications is required. The experiments on PPMI data demonstrate that, using the proposed methodology, we can identify some clinically confirmed patients’ symptoms suggesting medications change. In terms of predictive performance, our multitask predictive clustering tree approach is mostly comparable to the random forest multitask model, but has the advantage of model interpretability.     

Update on the risk of lymphoma following immunosuppressive therapy for inflammatory bowel disease

The care of inflammatory bowel disease has changed considerably with the introduction of a number of immunosuppressants including anti-metabolite and anti-TNF therapies. While efficacious, these medications also carry important risks, notably the potential risk of lymphoma. This risk is one of the most worrisome for both patients and physicians. Our current knowledge is still evolving; however, our understanding of what risks these drugs carry, both individually and synergistically, is critical in allowing informed decision making. In this article, we will describe the known lymphoma risks of commonly used immunosuppressant medications in inflammatory bowel disease, with an emphasis on non-Hodgkin’s lymphoma and hepatosplenic T-cell lymphoma.     

Angiotensin-converting enzyme 2 receptors,chronic liver diseases,common medications,and clinical outcomes in coronavirus disease 2019 patients

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), enters affected cells through the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in type II alveolar cells, enterocytes, and cholangiocytes. SARS-CoV-2 infection causes fever, dry cough, and breathing difficulty, which can progress to respiratory distress due to interstitial pneumonia, and hepatobiliary injury due to COVID-19 is increasingly recognized. The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression. The development of more severe clinical outcomes in patients with chronic liver diseases (CLD) with or without cirrhosis infected with SARS-CoV-2 has not been elucidated. Moreover, there is limited data related to common medications that affect the disease severity of COVID-19 patients. Additionally, ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified. This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications. Furthermore, the association between ACE2 receptor expression and disease severity in these patients is discussed.     

Modified Yupingfeng Formula for the Treatment of Stable Chronic Obstructive Pulmonary Disease: A Systematic Review of Randomized Controlled Trials

Background

Chronic obstructive pulmonary disease (COPD), is a very common disease of respiratory system. An increasing number of clinical trials on Yupingfeng formula in the management of stable COPD have been performed. However, the evidence base for it remains unknown. This review aims at assessing the efficacy, and safety of modified Yupingfeng formula in the treatment of stable COPD through a systematic review of all available randomized controlled trials.

Materials and Methods

Literature retrieval was conducted using four English databases (CENTRAL, PubMed, EMBASE, and ISI Web of Science), and four Chinese databases (CBM, CNKI, VIP, and WANFANG), from respective inception to January 2013, and supplemented with a manual search. Review authors independently extracted the trial data, and assessed the quality of each trial. Methodological quality was assessed by Cochrane risk of bias and Jadad''s scale. The following outcomes were evaluated: (1) lung function; (2) 6-minute walk distance (6MWD); (3) effective rate; (4) serum levels of IgA, IgG and IgE; and (5) adverse events. Data were analyzed using STATA 12.0 software.

Results

A total of nine studies involving 660, stable COPD patients were identified. Patients from all studies included in this review were randomized to receive Yupingfeng formula combined with Western medications in comparison with Western medications. In general, the methodological quality of the included trials was poor. The results of this systematic review indicates that, compared with Western medications alone, the use of Yupingfeng formula, if combined with Western medications could significantly improve FEV₁ (WMD = 0.30L; 95%CI: 0.19, 0.42), FEV₁/FVC ratio (SMD = 0.69; 95%CI: 0.48, 0.91), 6MWD (WMD = 31.73m; 95% CI: 19.29, 44.17), and effective rate (RR = 1.24; 95% CI: 1.10, 1.41), and increase the serum levels of IgA (WMD = 0.25; 95%CI: 0.16, 0.34) and IgG (WMD = 1.10; 95%CI: 0.53, 1.68), but no difference was found in the serum IgE levels (WMD = 0.47; 95%CI: −0.32, 1.27) between the two groups. No serious adverse events were reported.

Conclusions

Within the limitations of this systematic review, we may conclude that compared with Western medications alone, Yupingfeng formula, when combined with Western medications can provide more benefits for patients with stable COPD, without any serious adverse reactions being identified. However, these benefits need to be further confirmed through high-quality prospective placebo-controlled trials that should be strictly conducted in accordance with methodological principles and procedures.     

Pharmacogenomics: a new paradigm to personalize treatments in nephrology patients

Although notable progress has been made in the therapeutic management of patients with chronic kidney disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication‐related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non‐genetic and genetic factors responsible for the great inter‐patient variability in drugs metabolism, disposition and therapeutic targets. Over the years several genetic settings have been linked, using pharmacogenetic approaches, to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, analysing single gene or candidate pathways, do not represent the gold standard, being the overall pharmacological effects of medications and not typically monogenic traits. Therefore, to identify multi‐genetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole genomic high‐throughput technologies. However, to date, only few pharmacogenomics reports have been published in nephrology underlying the need to enhance the number of projects and to increase the research budget for this important research field. In the future we would expect that, applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic make‐up, to monitor carefully the efficacy/toxicity of a given drug and to modify the dosage or number of medications to obtain predefined clinical outcomes.     

Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy

Gastrointestinal symptoms are often an early and prominent manifestation of Fabry disease, an X-linked inborn error of metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. This enzyme deficiency results in the progressive accumulation of globotriaosylceramide and other glycosphingolipids in tissue lysosomes throughout the body. In classically affected patients, glycosphingolipid accumulation in the vascular endothelium eventually culminates in life-threatening renal, cardiac, and cerebrovascular disease. In addition, over 50% of patients experience post-prandial abdominal pain and diarrhea that interferes with the ability to work and quality of life. Here, we describe four males aged 17-40 years with classic Fabry disease and severe gastrointestinal symptoms who participated in clinical trials of enzyme replacement therapy with agalsidase beta (Fabrazyme, 1 mg/kg every 2 weeks). Before therapy, the three adult patients experienced post-prandial abdominal pain, bloating, and severe diarrhea with 7-10 bowel movements per day every day and the 17-year-old had weekly episodes of diarrhea with six bowel movements per day. Other symptoms included vomiting, food intolerance, and poor weight gain. All patients took medications for these symptoms (diphenoxylate-atropine [Lomotil], ranitidine hydrochloride [Zantac], or sulfasalazine). After 6-7 months of agalsidase beta therapy, all patients reported "no or only occasional" abdominal pain or diarrhea, had discontinued their gastrointestinal medications, and had gained 3-8 kg. These marked improvements in gastrointestinal symptoms have persisted for over 3 years of treatment. In such patients, enzyme replacement at 1 mg/kg effects an early and significant clinical improvement in the gastrointestinal manifestations of Fabry disease.     

农村冠心病患者自我管理水平特点及影响因素分析

目的 探究农村冠心病患者的自我管理特点,并分析其影响因素。方法 采用方便抽样法,选取长沙市中南大学湘雅医院心内科161例农村冠心病住院患者作为研究对象,分别采用冠心病自我管理量表、社会支持评定量表、简易应对方式问卷、慢性病管理自我效能量表来进行农村冠心病患者的自我管理水平测评。结果 农村冠心病患者自我管理得分为（56.97±9.80）分,单因素方差分析结果显示不同家庭月收入、同住家人、住院次数、是否长期服药、服药的种类不同的农村冠心病患者自我管理得分差异具有统计学意义（P＜0.05）。相关性分析结果显示:自我管理得分与社会支持得分、积极应对得分呈正相关;社会支持得分与积极应对得分呈显著正相关（P＜0.01）。逐步回归分析结果显示,长期服药种类数、积极应对、冠心病住院次数、自我效能和有无宗教信仰共5个因素进入回归方程（F=37.590,P=0.000）。结论 农村冠心病患者自我管理水平总体呈中等偏低水平,自我效能感、长期服药种类数、积极应对、冠心病住院次数、有无宗教信仰是影响农村冠心病患者自我管理的主要因素。     

Inflammatory bowel disease and pregnancy: an update

Women with inflammatory bowel disease have similar rates of conception to the general population unless they have had pelvic surgery. Once pregnant, regardless of disease activity, they have an increased risk of adverse pregnancy outcome and should be followed as high-risk obstetric patients. Most medications are compatible with pregnancy and lactation, as described in this article. Ideally, women should discuss their plans for pregnancy with their physician prior to conception so that risks and benefits can be reviewed, medications adjusted and healthcare maintenance updated. Once pregnant, a multidisciplinary team of gastroenterologists, obstetricians and pediatricians should help to ensure the best care for the mother and child.     

Environmental Pollution and Chronic Kidney Disease

Chronic kidney disease (CKD) is a global public health problem associated with high rates of morbidity and mortality due to end-stage renal disease and cardiovascular disease. Safe and effective medications to reverse or stabilize renal function in patients with CKD are lacking, and hence it is important to identify modifiable risk factors associated with worsening kidney function. Environmental pollutants, including metals, air pollutant, phthalate and melamine can potentially increase the risk of CKD or accelerate its progression. In this review, we discuss the epidemiological evidence for the association between environmental pollution and kidney disease, including heavy metals, air pollution and other environmental nephrotoxicants in the general population.     

Choroba Kikuchi i Fujimoto: opis dwóch nowych polskich przypadków i aktualny przegląd piśmiennictwa

Kikuchi-Fujimoto disease (KFD, histiocytic necrotizing lymphadenitis) is benign and self-limited cervical lymphadenopathy with accompanied mild fever. Disorder mostly affects young adults, rarely children mainly in Asia. The etiology of KFD is unknown but it is thought to be an autoimmune or inflammatory process triggered by viral infection in susceptible individuals. The minimal criteria required for the diagnosis of KFD include the presence of paracortical clusters of plasmacytoid dendritic cells admixed with karyorrhectic bodies and crescentic histiocytes. KFD does not require specific treatment except from antipyretics and anti-inflammatory medications. Here we present two new cases of KFD described in Poland together with the review of current literature.     

Impaired regulation of stride variability in Parkinson's disease subjects with freezing of gait

Patients with Parkinson's disease (PD) often experience freezing of gait, a debilitating phenomenon during which the subject suddenly becomes unable to start walking or to continue to move forward. Little is known about the gait of those subjects with PD who experience freezing of gait or the pathophysiology of freezing. One possibility is that freezing of gait is a truly paroxysmal phenomenon and that the usual walking pattern of subjects who experience freezing of gait is not different than that of other patients with PD who do not experience these transient episodes of freezing of gait. On the other hand, a recent study noted gait changes just prior to freezing and concluded that dyscontrol of the cadence of walking contributes to freezing. To address this question, we compared the gait of PD subjects with freezing of gait to PD subjects without freezing of gait. Given the potential importance of the dyscontrol of the cadence of walking in freezing, we focused on two aspects of gait dynamics: the average stride time (the inverse of cadence, a measure of the walking pace or rate) and the variability of the stride time (a measure of "dyscontrol," arrhythmicity and unsteadiness). We found that although the average stride time was similar in subjects with and without freezing, stride-to-stride variability was markedly increased among PD subjects with freezing of gait compared to those without freezing of gait, both while "on" (P<0.020) and "off" (P<0.002) anti-parkinsonian medications. Further, we found that increased gait variability was not related to other measures of motor control (while off medications) and levodopa apparently reduced gait variability, both in subjects with and without freezing. These results suggest that a paradigm shift should take place in our view of freezing of gait. PD subjects with freezing of gait have a continuous gait disturbance: the ability to regulate the stride-to-stride variations in gait timing and maintain a stable walking rhythm is markedly impaired in subjects with freezing of gait. In addition, these findings suggest that the inability to control cadence might play an important role in this debilitating phenomenon and highlight the key role of dopamine-mediated pathways in the stride-to-stride regulation of walking. Electronic Publication     

Immunostimulation in the era of the metagenome

Microbes are increasingly being implicated in autoimmune disease. This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated. The standard of care for autoimmune disease remains the use of medications that slow the immune response, while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response. Immunostimulation is complicated by a cascade of sequelae, including exacerbated inflammation, which occurs in response to microbial death. Over the past 8 years, we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease. This intervention, designed to stimulate the innate immune response, has required a reevaluation of disease progression and amelioration. Paramount is the inherent conflict between palliation and microbicidal efficacy. Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms. Further studies are needed, but they will require careful planning to manage this immunopathology.     

Sleep-disordered breathing and cardiovascular disease in the Bay Area Sleep Cohort

STUDY OBJECTIVES: To examine the relationship between sleep-disordered breathing (SDB) and cardiovascular disease among community-dwelling older adults. Previous studies have suggested relatively stronger associations between SDB and such morbidity in middle-aged, relative to elderly, populations. DESIGN: Cross-sectional analysis of an elderly ambulatory, non-clinic-based cohort (Bay Area Sleep Cohort, BASC) SETTING: Community population studied in a sleep laboratory PARTICIPANTS: One hundred twenty-nine older adults (mean [+/- SD] age = 72.6 [8.3]) (78 women; 51 men). INTERVENTIONS: NA. MEASUREMENTS: Complete clinical history including list of current medications, physical examination, selected blood chemistries, multiple blood pressure measurements, 12-lead electrocardiogram, and 2 consecutive nights of polysomnography. RESULTS: Fifty-one individuals (40%) were taking 1 or more cardiovascular medications and 24 (19%) had an apnea-hypopnea index (AHI) of 10 or more per hour of sleep. Cardiovascular medication use was related to cardiac events or procedures, history of angina, higher systolic or diastolic blood pressure, and abnormal electrocardiogram. Logistic regression showed statistically significant association between cardiovascular medication use and AHI of 10 or greater per hour, independent of age, sex, and body mass index. Supplementary analyses indicated that rapid eye movement AHI of 10 or greater per hour was significantly associated with elevated diastolic blood pressure. CONCLUSIONS: The results suggest that sleep-disordered breathing may contribute to increased cardiovascular morbidity in older adults.     

The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease

Linkage of the lipoprotein lipase (LPL) gene to blood pressure levels has been reported. The LPL S447X single nucleotide polymorphism (cSNP) has been associated with decreased triglycerides (TG), increased high density lipoprotein cholesterol, and a decreased risk of coronary artery disease (CAD), which may occur independently of its beneficial lipid changes. To investigate the relationship between LPL S447X cSNP and these parameters, we studied a cohort of individuals with familial hypercholesterolemia in whom blood pressures and information regarding the use of blood pressure lowering medications were available. Carriers of the S447X variant had decreased TG (1.21+/-0.47 vs. 1.52+/-0.67, p<0.001) and a trend towards decreased vascular disease (12.7 vs. 19.5%) compared to non-carriers. More interestingly, however, carriers of this cSNP had decreased diastolic blood pressure compared to non-carriers (78+/-10 vs. 82+/-11, p=0.002), evident in both men and women, youths and adults, with similar trends for systolic blood pressure. Furthermore, the decrease in blood pressure appeared independent of the decrease in TG (p=0.02), suggesting that the LPL protein may have a direct influence on the vascular wall. This suggests an additional mechanism whereby this variant may have protective effects, independent of changes in plasma lipid levels.     

Pharmacological treatment of acromegaly

Acromegaly is an endocrine disorder usually due to a growth hormone (GH)-secreting pituitary adenoma. This deforming disease is associated with several metabolic abnormalities and results in an elevated cardiovascular mortality. Pituitary transsesphenoidal surgery has been considered the treatment of choice, however, even in the most experienced hands this procedure succeeds in curing only 50 to 60% of the patients. Therefore, close to 50% of patients require an adjunctive form of treatment such as radiation therapy or the use of diverse medications that modulate GH secretion (somatostatin analogues) or action (GH receptor antagonists). The present review summarizes the clinical experience with these novel medications.     

RhD免疫性溶血产前诊断与治疗的研究

目的探讨应用荧光定量PCR方法对Rh阴性孕妇血浆中游离胎儿DNA;进行无创性产前诊断胎儿RhD血型及应用血浆置换疗法配合药物治疗孕妇及胎儿Rh(D)血型不合的免疫性溶血病的疗效,预防孕妇早孕自然流产或不足月死胎。方法产前采用荧光定量PCR技术产前检测胎儿RhD血型,分娩后用血清学方法证实。对照组14例用药物治疗孕妇及胎儿Rh(D)血型不合者,实验组15例用血浆置换配合药物治疗对孕妇及胎儿Rh(D)血型不合者进行治疗,观察IgG抗-D抗体效价以及新生儿直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验,胆红素。结果产前荧光定量PCR与产后血清学法Rh(D)血型结果一致。对照组14例孕妇孕期血浆抗体滴度为1∶32～1∶256;实验组15例孕妇PE 2～5次/例,血浆置换前后血浆抗体滴度分别为1∶(96±43.6)、1∶(18±14.7),二者比较有显著统计学差异(t=6.77,P<0.01)。对照组10例发生新生儿溶血病,实验组4例发生新生儿溶血病。对照组10例直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验均阳性,血清胆红素:(84.2～205)μmol/L,平均(154.6±46)μmol/L;实验组4例直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验阳性,血清胆红素:38.3μmol/L～141.2μmol/L,平均(76.5±36)μmol/L。结论应用荧光定量PCR方法进行无创性胎儿RhD血型检测可用于新生儿溶血病的预防和诊断;血浆置换配合药物治疗孕妇及胎儿RhD血型不合的免疫性溶血病的疗效优于单纯药物治疗,值得临床推广应用。     

Parkinson’s disease hand tremor detection system for mobile application

Parkinson’s disease currently affects millions of people worldwide and is steadily increasing. Many symptoms are associated with this disease, including rest tremor, bradykinesia, stiffness or rigidity of the extremities and postural instability. No cure is currently available for Parkinson’s disease patients; instead most medications are for treatment of symptoms. This treatment depends on the quantification of these symptoms such as hand tremor. This work proposes a new system for mobile phone applications. The system is based on measuring the acceleration from the Parkinson’s disease patient’s hand using a mobile cell phone accelerometer. Recordings from 21 Parkinson’s disease patients and 21 healthy subjects were used. These recordings were analysed using a two level wavelet packet analysis and features were extracted forming a feature vector of 12 elements. The features extracted from the 42 subjects were classified using a neural networks classifier. The results obtained showed an accuracy of 95% and a Kappa coefficient of 90%. These results indicate that a cell phone accelerometer can accurately detect and record rest tremor in Parkinson’s disease patients.     

WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease

Peroxisome proliferator-activated receptor alpha (PPARalpha) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0.05% WY14,643 or control food and immunized with the non-collagenous domain of the alpha3 chain of Type IV collagen [alpha3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARalpha ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80(+) macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARalpha ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-gamma mRNA expression in the WY14,643-fed mice, suggesting that the PPARalpha ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARalpha ligands may be a novel treatment for inflammatory renal disease.