Noninvasive Home Mechanical Ventilation in Adult Myotonic Dystrophy Type 1:A Systematic Review

Introduction: Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients. Methods: A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis. Results: Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure. Conclusion: This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance

Rationale, description and baseline findings of a community-based prospective cohort study of kidney function amongst the young rural population of Northwest Nicaragua.

BACKGROUND: An epidemic of Mesoamerican Nephropathy (MeN) is killing thousands of agricultural workers along the Pacific coast of Central America, but the natural history and aetiology of the disease remain poorly understood. We have recently commenced a community-based longitudinal study to investigate Chronic Kidney Disease (CKD) in Nicaragua. Although logistically challenging, study designs of this type have the potential to provide important insights that other study designs cannot. In this paper we discuss the rationale for conducting this study and summarize the findings of the baseline visit. METHODS: The baseline visit of the community-based cohort study was conducted in 9 communities in the North Western Nicaragua in October and November 2014. All of the young men, and a random sample of young women (aged 18-30) without a pre-existing diagnosis of CKD were invited to participate. Glomerular filtration rate (eGFR) was estimated with CKD-EPI equation, along with clinical measurements, questionnaires, biological and environmental samples to evaluate participants' exposures to proposed risk factors for MeN. RESULTS: We identified 520 young adults (286 males and 234 females) in the 9 different communities. Of these, 16 males with self-reported CKD and 5 females with diagnoses of either diabetes or hypertension were excluded from the study population. All remaining 270 men and 90 women, selected at random, were then invited to participate in the study; 350 (97%) agreed to participate. At baseline, 29 (11%) men and 1 (1%) woman had an eGFR <90 mL/min/1.73 m2. CONCLUSION: Conducting a community based study of this type requires active the involvement of communities and commitment from local leaders. Furthermore, a research team with strong links to the area and broad understanding of the context of the problem being studied is essential. The key findings will arise from follow-up, but it is striking that 5% of males under aged 30 had to be excluded because of pre-existing kidney disease, and that despite doing so 11% of males had an eGFR <90 mL/min/1.73 m2 at baseline

Change over time in ability to perform activities of daily living in myotonic dystrophy type 1

Objective: The objective of this longitudinal, observational study was to investigate change over time in ability to perform activities of daily living in myotonic dystrophy type 1 (DM1). Methods: Adults with genetically confirmed DM1 were recruited as part of the PhenoDM1 study in the UK. Data on activities of daily living were recorded through the DM1-ActivC at baseline and a follow-up visit after 12 (± 3) months. A subset of patients had advanced genetic testing to determine the size of the progenitor allele. Results: Our sample comprised 150 patients with DM1 (mean age: 45 years; 52% female). Mean follow-up was 383 days. Mean DM1-ActivC total score at baseline was 71.24 (95% confidence interval 67.77–74.71) and at the follow-up visit 69.04 (65.54–72.54). Approximately 43% of patients had a lower score at the follow-up visit (indicating a decreased ability to perform activities of daily living), 24% a higher score (indicating an increased ability), and 33% the same score at baseline and follow-up. The mean annual change in the DM1-ActivC total score, estimated at − 2.06 (− 3.54 to − 0.59), was significantly related to patients’ baseline score, but not sex, disease duration, timed test results, or cytosine-thymine-guanine repeat length. Conclusions: Change over time in ability to perform activities of daily living as recorded through the DM1-ActivC varies substantially between patients with DM1. Our data contribute to the understanding of the natural evolution of the disease, and should be helpful to inform the design of future trials based on the DM1-ActivC

Deliberative Democracy in the EU. Countering Populism with Participation and Debate. CEPS Paperback

Elections are the preferred way to freely transfer power from one term to the next and from one political party or coalition to another. They are an essential element of democracy. But if the process of power transfer is corrupted, democracy risks collapse. Reliance on voters, civil society organisations and neutral observers to fully exercise their freedoms as laid down in international human rights conventions is an integral part of holding democratic elections. Without free, fair and regular elections, liberal democracy is inconceivable. Elections are no guarantee that democracy will take root and hold, however. If the history of political participation in Europe over the past 800 years is anything to go by, successful attempts at gaining voice have been patchy, while leaders’ attempts to silence these voices and consolidate their own power have been almost constant (Blockmans, 2020). Recent developments in certain EU member states have again shown us that democratically elected leaders will try and use majoritarian rule to curb freedoms, overstep the constitutional limits of their powers, protect the interests of their cronies and recycle themselves through seemingly free and fair elections. In their recent book How Democracies Die, two Harvard professors of politics write: “Since the end of the Cold War, most democratic breakdowns have been caused not by generals and soldiers but by elected governments themselves” (Levitsky and Ziblatt, 2018)

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy.

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease

Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7

<p>Abstract</p> <p>Background</p> <p>Sodium channel Na_V1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na_V1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na_V1.7/I228M variant.</p> <p>Methods</p> <p>We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na_V1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p> <p>Results</p> <p>We report three different clinical presentations of the I228M Na_V1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na_V1.7 variant, two of which are from a single family. We also demonstrate that the Na_V1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p> <p>Conclusion</p> <p>Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na_V1.7.</p

Prostate-specific antigen (PSA) screening and follow-up investigations in Māori and non-Māori men in New Zealand

Text. Pairwise sequence alignment between human SCN9A and homologous genes. (DOCX 34 kb

Vibration threshold in non-diabetic subjects

Measuring vibration perception threshold (VPT) accurately classifies and quantifies the severity of loss of vibration perception. A biothesiometer (Bio-thesiometer®; Bio Medical Instrument Co, Ohio, USA) appears to be the most suitable tool to determine VPT due to its low inter-rater variability and low occurence of adaption to the sensation. Different VPT values for a biothesiometer have been described, however, specification on age, height and different measurement locations is currently lacking. The objective of our study was to identify determinants of vibration perception in non-diabetic subjects, in order to provide individualized normal values of VPTs for clinical practice. Measurements of the vibration perception were performed on the big toes, insteps, lateral malleoli, and wrists. A total of 205 healthy subjects were included (108 (52.7%) males) with a median [interquartile range] age of 59 [51;64] (range 21-80) years. Mean height was 174.45 ± 9.20 cm and mean weight was 82.94 ± 14.84 kg, resulting in a mean BMI of 27.19 ± 4.00 kg/m2. In stepwise forward linear regression analyses, age (st. β = 0.51, p < 0.001) and height (st. β = 0.43, p < 0.001) were found to be the independent unmodifiable determinants of the VPT at the big toe. Regression coefficients for quantiles of the determinants age and height were incorporated in the corresponding regression equations. This study provides equations to calculate age- and height-specific normal values for VPT that can be used in clinical practice and in large research studies

Konseptual Framework Untuk Pengukuran Kualitas Website Pada Sistem Informasi Akademik Dengan Metode Gqm

Konseptual framework yang diusulkan dalam penelitian ini berupa model konseptual yang merupakan gambaran proses pengukuran kualitas beserta tahapan yang dilakukan dalam pengukuran kualitas website sistem informasi akademik. Model konseptual yang sudah ada selama ini masih bersifat luas dan tidak spesifik pada domain tertentu. Terdapat banyak website yang dibangun oleh web developer, namun masih sedikit yang dibangun sesuai dengan kebutuhan pengguna. Salah satu website online dibidang pendidikan adalah sistem informasi akademik. Sistem informasi akademik merupakan layanan website oleh universitas dalam menyediakan informasi dan pengelolaan data-data akademik. Karakteristik dari sistem informasi akademik adalah academic content, periodic acccessibility, level of user authority, precission dan accurateness. Beberapa dari karakteristik tersebut kemudian dipetakan kedalam faktor-faktor kualitas yang diadopsi dari berbagai model, seperti ISO-9126, Website quality Model, dan academic website quality model. akademik. Hasil pemetaan tersebut memperoleh 5 faktor kualitas yang diusulkan untuk melakukan pengukuran kualitas, yaitu USAbility, functionality, content, efficiency dan reliability. Kelima faktor kualitas ini dijadikan sebagai tujuan pengukuran. Metode GQM digunakan untuk memperoleh metric internal agar menghasilkan pengukuran yang objektif dan kuantitatif. Metric-metric yang dihasilkan dari metode GQM divalidasi dengan menggunakan validasi empiris. Metric internal produk diterapkan dalam studi kasus sistem informasi akademik berbasis web universitas di Pekanbaru. Hasil validasi dari framework pengukuran yang dibangun adalah memiliki nilai baik pada faktor kualitas functionality, content dan reliability, dan nilai cukup pada faktor kualitas USAbility dan efficiency