Technical evaluation and usability of a quantitative G6PD POC test in cord blood: a mixed-methods study in a low-resource setting.

OBJECTIVES: New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for Plasmodium vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. METHODS: We conducted a mixed-methods study analysing technical performance and usability of the 'STANDARD G6PD' Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border. RESULTS: In 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95% CI: 0.859 to 1.000) and a specificity of 0.993 (95% CI: 0.971 to 0.999) as compared with gold-standard spectrophotometry to diagnose G6PD-deficient newborns using a receiver operating characteristic (ROC) analysis-derived threshold of ≤4.8 IU/gHb. The Biosensor had a sensitivity of 0.727 (95% CI: 0.498 to 0.893) and specificity of 0.933 (95% CI: 0.876 to 0.969) for 30%-70% activity range in girls using ROC analysis-derived range of 4.9-9.9 IU/gHb. These thresholds allowed identification of all G6PD-deficient neonates and 80% of female neonates with intermediate phenotypes.Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor.Focus group discussions found high levels of learnability, willingness, satisfaction and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early ('We can know that early, we can counsel the parents about the chances of their children getting jaundice') and at the POC, including in more rural settings ('Because we can know the right result of the G6PD deficiency in a short time, especially for the clinic which does not have a lab'). CONCLUSIONS: The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia.

A Case of Narcolepsy Type 2 and Postural Tachycardia Syndrome Secondary to Lesions of the Thalamus and Amygdala.

ABSTRACT: Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

[Diagnostic and therapeutic update in narcolepsy]. / Actualizacion diagnostica y terapeutica en narcolepsia.

Narcolepsy is an emblematic, unique disease within sleep disorders that is characterised by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep. In the last 14 years truly spectacular progress has been made in our knowledge of this disease, since the discovery of its cause, i.e. a loss of the hypothalamic neurons that synthesise hypocretin, a previously unknown neurotransmitter, and its probable aetiopathogenic mechanisms, i.e. an autoimmune process in a patient with very precise immunological characteristics - a specific type of HLA and a specific type of T-cell receptor. The cause of this autoimmune process remains unknown. The definitive treatment - the administration of hypocretin, which is the substance missing in the organism - is still unavailable, but there are powerful drugs for treating its main symptoms, the sleepiness and the cataplexy. Some of these are classic compounds (methylphenidate, clomipramine), while others are more recent (modafinil, venlafaxine, sodium oxybate), but together they allow many patients to experience significant improvements. Lack of knowledge about the disease, both on the part of patients and their relatives as well as physicians, is the reason for the great delay in its diagnosis, with even more dramatic consequences when the disease begins in infancy.

Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is characterized by loss of the normal muscle atonia during REM sleep associated with disruptive motor activity related to the acting out of dreams. There is frequently injury to the patient or bed partner, and treatment is usually required. Clonazepam has been the first-line therapy for many years, with 2 large case series reporting efficacy with few side effects in the majority of patients. However, long-acting hypnotics in the elderly or those with cognitive impairment can be associated with adverse events especially unacceptable daytime sedation, confusion, and exacerbation of existing sleep apnea. METHODS: We reviewed 39 patients with confirmed RBD who were treated within our regional sleep center, assessing both efficacy and side effects of drug therapies. RESULTS: Adverse effects were reported by 58% of the patients using clonazepam, with 50% either discontinuing the drug or reducing the dose. This prompted us review the side effects of clonazepam in detail and to look for alternative therapies. We report several novel and effective therapies, in particular zopiclone, in a series of patients under long-term follow-up for RBD. CONCLUSIONS: There are alternatives to clonazepam therapy for RBD which can be as effective and may be better tolerated.

[The effect of a new phenylalkyl taurine derivative on the size of the necrotic area in experimental myocardial infarct in rats]. / Vliianie novogo fenilalkil'nogo proizvodnogo taurina na razmer zony nekroza pri éksperimental'nom infarkte miokarda u krys.

The study of an anti-ischemic action of a new phenilalkyl taurin derivative TAU-60 has discovered that this drug attenuates ECG signs of myocardial infarction and reduces the size of necrosis zone on the anterior wall of the left ventricular myocardium in rats with experimental myocardial infarction.

[The action of sodium oxybutyrate and emoxypin on the functional state of the adrenaline-damaged myocardium in an experiment]. / Deistvie natriia oksibutirata i émoksipina na funktsionnal'noe sostoianie povrezhdennogo adrenalinom miokarda v éksperimente.

The effect of agents possessing antihypoxic and antioxidant activity, namely sodium oxybutyrate and emoxypin, on the functional state of the heart muscle was studied in experiments on dogs with epinephrine necroses of the myocardium. A marked cardioprotective effect was produced by sodium oxybutyrate infused intravenously (200 mg/kg) either 10 min or 2 hrs after myocardial damage had been modelled and by emoxypin (4 mg/kg; 0.4 mg/kg) infused intravenously 30 min after the damage.

[Changes in the morphofunctional status of the liver in rats with acute tetrachloromethane poisoning and their correction with antihypoxants, antioxidants and actoprotectors]. / Izmeneniia morfofunktsional'nogo sostoianiia pecheni krys pri ostroi intoksikatsii tetrakhlormetanom i ikh korrektsiia antigipoksantami, antioksidantami i aktoprotektorami.

The acute tetrachlormethane intoxication leads to structural and metabolic alterations in the rat liver. Morphological changes include centrolobular necroses and blood stasis in dilated sinusoidal capillaries. Metabolic changes are manifested by an increase in the water content and time of the spin-lattice (T1) and spin-spin (T2) relaxation (this indicates a lesser degree of water structuralization and its enhanced lability), and distortion of the correlation between T1 and T2. The prophylactic administration of one of the antihypoxants, antioxidants or actoprotectors normalizes the morphofunctional condition of the liver. According to the degree of the therapeutic efficacy, the examined preparations form the following series: dibunol > gamma-sodium hydroxybutyrate > tomerzol.

[The action of piracetam and its complex with sodium oxybutyrate in the neuropathic pain syndrome]. / Deistvie piratsetama i ego kompleksa s oksibutiratom natriia pri neiropaticheskom bolevom sindrome.

Effects of the pyracetam and its sodium hydroxybutyrate complex were studied on a model of the neuropathic pain syndrome. It was demonstrated that the pyracetam prevents the development of the neuropathic pain syndrome. The pyracetam relieves the pain syndrome. The sodium hydroxybutyrate appears to enhance preventive and medical effects of the pyracetam. Possible mechanisms of action of these drugs are discussed.

[A pharmacological analysis of the antiedematous action of GABA-ergic and opioidergic agents in craniocerebral trauma]. / Farmakologicheskii analiz protivootechnogo deistviia GAMK- i opioidergicheskikh sredtsv pri cherepno-mozgovoi travme.

Experiments on rats with skull inquiry show that biculline (dose 2 mg/kg) removes antiedematous effect of fenibut (50 mg/kg), sodium hydroxybutirate (200 mg/kg), promedol (1 mg/kg), and synthetic analogs of encephalines DAGO and DSLET (100 mg/kg). Naloxon at a dose 1 mg/kg blocks antiedematous effect of ligands of opiate receptors, but does not change the effect of fenibut and sodium hydroxybutirate. The presence of close inter-regulatory interactions between GAMK-ergic and opioidergic systems in forming the traumatic correction is suggested.

Acetato de desmopresina en niños enuréticos resistentes a terapias convencionales / Desmopressin acetate in children with conventional therapy resistant enuresis

Se describen los resultados obtenidos con acetato de desmopresina en aerosol por inhalación nasal en 29 niños (15 varones) entre 8 y 10 años de edad, que sufrían enuresis nocturna resistente a tratamiento con imipramina sola y/o asociada a ácido oxibutinino. En todos ellos la anatomía y función vesical eran normales y ninguno sufría enfermedades neurológicas o renales. La desmopresina se suministró en dosis diarias de 10 µg que fueron aumentadas semanalmente, si era necesario, en igual proporción, hasta obtener uno o ningún episodio semanal de enuresis o un máximo de 40 µg diarios del fármaco. La dosis así titulada se mantuvo por 3 meses, al cabo de los cuales se redujo progresivamente en 10 µg semanales hasta suspenderla. Los pacientes fueron seguidos hasta un mes después de la supresión del tratamiento. Se obtuvo buen éxito (uno o menos episodios de enuresis por semana) en 65 por ciento de los casos. Un mes después de suspender la desmopresina se registraban 62,2 por ciento de niñoscon uno o menos episodios semanales de enuresis, sugiriendo una baja proporción de recaídas en plazos cortos. No se anotaron efectos colaterales importantes duarnte el estudio en este grupo de niños, salvo cefalea persistente en un paciente con antecedentes de jaqueca

[The comparative efficacy of emoxipine and sodium oxybutyrate in experimental myocardial ischemia]. / Sravnitel'naia éffektivnost' émoksipina i oksibutirata natriia pri eksperimental'noi ishemii miokarda.

The efficacy of emoxypine (2-ethyl-6-methyl-3-hydroxypyridine chlorohydrate) versus sodium hydroxybutyrate in total and local ischemia followed by reperfusion was studied in the experiments on rat isolated hearts. Emoxypine in a dose of 1 nM in total ischemia was shown to have a protective action, by decreasing reperfusion contracture. In local ischemia, emoxypine, unlike sodium hydroxybutyrate, did not favour greater restoration of the amplitude of isolated heart contractions, but restored coronary flow and stabilized contraction frequency better than did sodium hydroxybutyrate.

Possible involvement of a gamma-hydroxybutyric acid receptor in startle disease.

Startle disease or hyperreflexia is an autosomal dominant neurological disorder, with a neonatal onset, characterized by muscular hypertonia and myoclonic jerks, exaggerated by the slightest stimulus. Low concentrations of free gamma-aminobutyric acid (GABA) have been found in the cerebrospinal fluid of two affected infants. The involvement of GABA or its receptors has been raised and the use of GABA-agonist drugs has been suggested. We report a newborn with startle disease who also had a low concentration of GABA in the cerebrospinal fluid. No clinical improvement was observed with progabide, a GABA agonist. Furthermore, a high dose (100 mg/kg) of gamma-hydroxybutyrate (GHB) did not improve muscular stiffness and failed to induce general anesthesia. GHB, currently used as an effective general anaesthetic, is a structural analogue of GABA. It is present naturally at low concentrations in the brain and is regarded as an inhibitory neurotransmitter. Two specific GHB receptors, distinct from the GABA receptors, have been identified in rat brain. Failure to induce general anesthesia with a high dose of GHB suggests that one of these receptors could be involved in startle disease.

[Sodium oxybutyrate normalizes the central nervous system functions in the progeny of rats subjected to hypobaric hypoxia during pregnancy]. / Natriia oksibutirat mormalizuet funktsii tsentral'noi nervnoi sistemy u potomstva krys, podvergshikhsia gipobaricheskoi gipoksii vo vremia beremennosti.

Two-hour hypobaric hypoxia of rats on day 15 of their pregnancy led to a reduction in weight gain of pups within 20 days after birth, disturbed memory in active and passive paradigms, changed adaptive behavior in the extrapolatory water avoidance test, and impaired sleep in adult animals. Postnatal treatment with sodium hydroxybutyrate given in a dose of 50 mg/kg/day on days 8 to 20 of life normalized mnestic functions of the brain, the process of falling asleep, and physical development which had been impaired by intrauterine hypoxia.

[Cerebral protection]. / Protezione cerebrale.

Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral metabolic standpoint, exposure to isoflurane at concentration of 2 MAC is credited with providing the same potential for protection as high dose barbiturate (isoelectric EEG). A possible major difference between barbiturates and isoflurane is the modest cerebral vasodilation induced by the latter while barbiturates are associated with decreased CBF. This suggests that in focal ischemia isoflurane may elicit an intracerebral steal. 3) Calcium entry blockers. Some calcium entry blockers with the distinctive feature of acting preferably on cerebral as opposed to systemic vascular smooth muscles may exert beneficial effects during or after brain ischemia. Two such drugs which have shown promise are nimodipine and lidoflazine. In animal and human studies nimodipine has been reported to improve the neurologic outcome of both the cerebral vasospasm and the postischemic hypoperfusion state.(ABSTRACT TRUNCATED AT 400 WORDS)

[The correction of postvagotomy disorders of the motor function in the small intestine by using antihypoxants and antioxidants]. / Korrektsiia postvagotomicheskikh barushenii dvigatel'noi funktsii tonkoi kishki s pomoshch'iu antigipoksantov i antioksidantov.

Study of the electric activity of small intestine smooth muscle in vagotomized rats demonstrated diminution and disturbance of intestinal motility. These changes were most expressed within 30 days after vagotomy. Injection of antihypoxant sodium gamma-oxybutyrate and antioxidant dibunol to the vagotomized rats resulted in normalization of intestinal motility.

[The long-term use of antihypoxants in myocardial infarct in rats: their effect on the hemodynamics and contractile function of the heart]. / Dlitel'noe primenenie antigipoksantov pri infarkte miokarda u krys: vliianie na gemodinamiku i sokratitel'nuiu funktsiiu serdtsa.

In the experiments in rats with myocardial infarction induced by left coronary occlusion, effects of antihypoxants were studied during their long-term intraperitoneal injection (daily once during 21 days) on hemodynamics and myocardial contractility. Sodium oxybutyrate, 200 mg/kg, piracetam, 400 mg/kg, and glyo-6, 100 mg/kg, were shown to exert no significant effects on cardiac contractility at rest, however during exercise they normalized aortic blood flow acceleration. The antihypoxants increased the survival of rats with myocardial infarction.

[The radioprotective effect of GABA-tropic substances, gamma-hydroxybutyrate and piracetam]. / Issledovanie radiozashchitnogo éffekta GAMK-tropnykh veshchestv, gamma-gidroksibutirata i piratsetama.

From experiments in mice, it is shown that with a radiation dose of 8 Gy (LD96) the radioprotective effect was exerted by gamma-aminobutyric acid (GABA), substances that increase its concentration in tissues (progabide and valproate), and synthetic agonists of both receptor types, particularly baclofen, a GABA-receptor agonist. The radioprotective effect is also exerted by gamma-hydroxybutyrate, not piracetam.