The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population.

INTRODUCTION: Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. METHODS: The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). RESULTS: In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p < 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p < 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p < 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p < 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. CONCLUSION: A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.

People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population: Analysis of Two Observational Studies.

INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. METHODS: MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. RESULTS: In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). CONCLUSION: This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.

Long-term use of carglumic acid in methylmalonic aciduria, propionic aciduria and isovaleric aciduria in Italy: a qualitative survey.

OBJECTIVE: Organic acidurias (OAs) are a group of rare metabolic disorders that disrupt the regular amino acid metabolism. OAs are characterized by recurrent episodes of acidemia, ketonuria and hyperammonemia which can result in brain/liver damage and renal failure, and despite the life-long protein-restricted diet, impaired growth and long-term complications can occur. Consequently, a long-term management of OAs patients is required, aimed principally at reducing the frequency and duration of metabolic decompensation/hyperammonemia episodes. Nevertheless, unlike the acute phase, evidence on the chronic management of OAs patients is less consolidated. SUBJECTS AND METHODS: To expand the knowledge on this field, 13 Italian referral centers for the management of OAs were involved in a survey focused on the long-term use of carglumic acid (Carbaglu®, Recordati Rare Diseases). RESULTS: Participating centers reported a reduction between 69% and 81% in the annual number of metabolic decompensations with the chronic use of carglumic acid and an improvement in protein intake. Most centers reported no difficulty using carglumic acid as a long-term therapy, along with a great compliance. CONCLUSIONS: Taken together, obtained data align with the available literature and support a positive clinical experience with the long-term carglumic acid administration. Additional studies aimed at better defining a proper dosage for the chronic administration of carglumic acid and the clinical and biochemical characteristics of patients treated chronically are needed. In addition, the potential impact of this treatment regimen on the neurological development and growth of patients should be elucidated.

Analysis of risk factors associated with gas embolism and evaluation of predictors of mortality in 482 loggerhead sea turtles.

Sea turtles that are entrapped in static and towed nets may develop gas embolism which can lead to severe organ injury and death. Trawling characteristics, physical and physiologic factors associated with gas-embolism and predictors of mortality were analysed from 482 bycaught loggerheads. We found 204 turtles affected by gas-embolism and significant positive correlations between the presence of gas-embolism and duration, depth, ascent rate of trawl, turtle size and temperature, and between mortality and ascent time, neurological deficits, significant acidosis and involvement of > 12 cardiovascular sites and the left atrium and sinus venosus-right atrium. About 90% turtles with GE alive upon arrival at Sea Turtle Clinic recovered from the disease without any supportive drug therapy. Results of this study may be useful in clinical evaluation, prognostication, and management for turtles affected by gas-embolism, but bycatch reduction must become a priority for major international organizations. According to the results of the present study the measures to be considered to reduce the catches or mortality of sea turtles for trawling are to be found in the modification of fishing nets or fishing operations and in greater awareness and education of fishermen.

Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report.

BACKGROUND: We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). CASE PRESENTATION: A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. CONCLUSIONS: This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway.

Treating phenylketonuria: a single centre experience.

Hyperphenylalaninaemia (HPA) is an inherited disorder that results in raised plasma phenylalanine levels with a range of severities, including phenylketonuria (PKU). Since the first attempts at treatment using a low-phenylalanine diet and after more than 50 years of research, considerable progress has been made so we are now at a stage where mental retardation caused by high plasma phenylalanine can be prevented. We must, however, be aware of the new challenges we face in managing PKU. These include: maintaining optimal growth by providing enough phenylalanine without jeopardizing the child's psychomotor development; providing an optimal nutritional status that ensures other essential nutrients, such as long chain polyunsaturated fatty acids, are not excluded from the diet; ensuring optimal compliance to the dietary intervention; and considering patients' quality of life. New strategies, such as tetrahydrobiopterin (BH4) supplementation, need to be evaluated with regard to safety, efficacy and expected outcomes in specific types of HPA.

Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice.

In this crossover study in 12 healthy volunteers, coadministration of amprenavir (1,200 mg; single dose) with grapefruit juice slightly reduced the maximum concentration of drug in serum (Cmax) compared to administration with water (7.11 versus 9.10 microg/ml), slightly increased the time to Cmax (1.13 versus 0.75 h), and did not affect the area under the concentration-time curve from 0 to 12 h (AUC(0-12)), the AUC(0-infinity), or the concentration at 12 h. Therefore, grapefruit juice does not clinically significantly affect amprenavir pharmacokinetics.

[Cardiopathies, pregnancy and labor in our hospital practice. Clinical cases from 1969 to 1987]. / Cardiopatie, gravidanza e parto nella nostra practica ospedaliera. Casistica clinica dal 1969 al 1987.

The behaviour of cardiopathies and the prognosis for labour was studied in 44 pregnant women with heart disease admitted to Muscatello Hospital Augusta in 1969-87. Improved cardiological and obstetric treatment together with the interdisciplinary approach adopted since 1971 eliminated maternal deaths and drastically reduced complications in pregnancies. Caesarian section was adopted in all but class I cases and was well tolerated. Puerperium passed without incident and the patients were up by the second or third day, released on day 8. There was also a distinct improvement in foetal prognosis with fewer small for date births and only one death due to foetal immaturity.

[Usefulness and limitations of hormonal monitoring of pregnancy with HPL and estriol in improving fetal prognosis and preventing neonatal neurologic deficiency]. / Utilità e limiti del monitoraggio ormonale della gravidanza con HPL ed estriolo nel miglioramento della prognosi fetale e nella prevenzione del deficit neurologico neonatale.

This multidisciplinary research has been subdivided into two parts. The first examines prognosis of the foetus and its weight development in relation to changes in the hormonal curves of HPL and E3 carried out in a batch of 339 3rd term pregnancies. A very high incidence of small-for-date newborns (30-64%) was noted in mothers with low hormonal values and generally a more frequent onset of hypoxia in pregnancy and in labour. The second part assesses the neurological profile of children born to the same mothers examined in the first part up to the 4th year of life. A neurological deficiency of a different extent was evidenced in 33.3% of the children born to mothers with low hormonal values in pregnancy, especially among those born underweight. The neurological deficiency in the control sample was 7.84%.

Distribution and pharmacological properties of the GABAA/benzodiazepine/chloride ionophore receptor complex in the brain of the fish Anguilla anguilla.

In the present study, we characterized the distribution and the pharmacological properties of the different components of the GABAA receptor complex in the brain of the eel (Anguilla anguilla). Benzodiazepine recognition sites labeled "in vitro" with [3H]flunitrazepam ([3H]FNT) were present in highest concentration in the optic lobe and in lowest concentration in the medulla oblongata and spinal cord. A similar distribution was observed in the density of gamma-[3H]aminobutyric acid ([3H]GABA) binding sites. GABA increased the binding of [3H]FNT in a concentration-dependent manner, with a maximal enhancement of 45% above the control value, and, vice versa, diazepam stimulated the binding of [3H]GABA to eel brain membrane preparations. The density of benzodiazepine and GABA recognition sites and their reciprocal regulation were similar to those observed in the rat brain. In contrast, the binding of the specific ligand for the Cl- ionophore, t-[35S]butylbicyclophosphorothionate ([35S]TBPS), to eel brain membranes was lower than that found in the rat brain. In addition, [35S]TBPS binding in eel brain was less sensitive to the inhibitory effects of GABA and muscimol and much more sensitive to the stimulatory effect of bicuculline, when compared with [35S]TBPS binding in the rat brain. Moreover, the uptake of 36Cl- into eel brain membrane vesicles was only marginally stimulated by concentrations of GABA or muscimol that significantly enhanced the 36Cl- uptake into rat brain membrane vesicles. Finally, intravenous administration of the beta-carboline inverse agonist 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methyl ester (20 mg/kg) and of the chloride channel blocker pentylenetetrazole (80 mg/kg) produced convulsions in eels that were antagonized by diazepam at doses five to 20 times higher than those required to produce similar effects in rats. The results may indicate a different functional activity of the GABA-coupled chloride ionophore in the fish brain as compared with the mammalian brain.