Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy.

PURPOSE: To examine diagnostic reference levels (DRL) and achievable doses (AD) of image-guided and size-specific dose estimates (SSDE) and organ and effective doses of CT-guided intrathecal nusinersen administration to adult patients with spinal muscular atrophy (SMA). METHODS: This study involved a total of 60 image-guided intrathecal nusinersen treatments between August 2017 and June 2018. Patient cohort comprised 14 adult patients with the following SMA types: type 2 (n = 9) and type 3 (n = 5) with a mean age of 33.6 years (age range 25-57 years). DRL, AD, SSDE, organ, and effective doses were assessed with a dose-monitoring program based on the Monte Carlo simulation techniques. RESULTS: DRL and AD for computed tomography are summarised as follows: in terms of CT-dose index (CTDIvol), DRL 56.4 mGy and AD 36.7 mGy; in terms of dose-length product (DLP), DRL 233.1 mGy cm and AD 120.1 mGy cm. DRL and AD for fluoroscopic guidance were distributed as follows: in terms of dose-area product (DAP), DRL 239.1 µGy m2 and AD 135.2 mGy cm2. Mean SSDE was 9.2 mGy. Mean effective dose of the CT-guided injections was 2.5 mSv (median 2.0 mSv, IQR 1.3-3.2 mSv). Highest organ doses in the primary beam of radiation were the small intestine 12.9 mSv, large intestine 9.5 mSv, and ovaries 3.6 mSv. CONCLUSION: Radiation exposure of SMA patients measured as DRLs is generally not higher compared with patients without SMA despite severe anatomical hazards. Dose monitoring data may allow clinicians to stratify radiation risk, identify organs at risk, and adopt measures for specific radiation dose reduction.

Dynamic discriminant model for predicting respiratory distress at birth based on mass volume ratio in fetuses with congenital lung malformation.

OBJECTIVES: The congenital lung malformation volume ratio (CVR) is a prenatal ultrasound measurement that parameterizes congenital lung malformation (CLM) size. The aims of this study were to use serial measurements to create estimated growth curves of fetal CVR for asymptomatic and symptomatic neonates with CLM and to investigate whether a discriminant prognostic model based on these measurements could predict accurately which fetuses with CLM will require invasive respiratory support at delivery and should therefore be delivered at a tertiary-care facility. METHODS: This was a retrospective study of fetuses diagnosed prenatally with CLM at three tertiary-care children's hospitals between 2009 and 2016. Those with two or more sonographic measurements of CVR were included. Serial fetal CVR measurements were used to create estimated growth curves for neonates with and those without respiratory symptoms at delivery, defined as requiring invasive respiratory support for the first 24 h after delivery. A discriminant model based on serial CVR measurements was used to calculate the dynamic probability of the need for invasive respiratory support. The performance of this model overall and in preterm and term neonates was compared with those using maximum CVR thresholds of 1.0 and 1.6. RESULTS: Of the 147 neonates meeting the inclusion criteria, 16 (10.9%) required postnatal invasive respiratory support. The estimated CVR growth curve models showed different growth trajectories for asymptomatic and symptomatic neonates, with significantly higher CVR in symptomatic neonates, and values peaking late in the second trimester at around 25 weeks' gestation in asymptomatic neonates. All prognostic methods had high accuracy for the prediction of the need for invasive respiratory support in term neonates, but the discriminant model had the best performance overall (area under the receiver-operating characteristics curve (AUC) = 0.88) and in the preterm population (AUC = 0.85). CONCLUSIONS: The estimated CVR growth curves showed different growth patterns in asymptomatic and symptomatic neonates with CLM. The dynamic discriminant model performed well overall and particularly in neonates that were carried to term. Development of an externally validated clinical tool based on this analysis could be useful in determining the site of delivery for fetuses with CLM. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

[The second stage of the Nursing Insurance Act and its effects on the institutional care within welfare for the elderly]. / Auswirkungen der 2. Stufe des Pflegeversicherungsgesetzes auf die Versorgung im stationären Bereich der Altenhilfe.

OBJECTIVE: The intention of the recently introduced compulsory nursing care insurance in Germany has been to support patients as well as relatives, and to reduce the burden on the social insurance system in financing professional services. In this study we examine the consequences of the 2nd stage of this legislation upon the care in old people's homes. METHODS: The investigation covered 5 institutions comprising two components: 1) Analysis of the records kept by the administration (N = 369), and 2) analysis of the volume of nursing care in a sample of N = 121 (including basic care as well as psychosocial support) provided by the staff over a period of 14 days. RESULTS: The required volume of basic nursing care (SGB XI) determines the classification of patients according to their need for nursing. Although by law the amount of nursing in stage 0 should be none, nevertheless 20 minutes of basic care in average are provided each day here. In stages II and III the observed nursing-time exceeded the allowed values slightly. In stage III realized nursing was far below the legal provision, although the private co-payments were highest. CONCLUSION: The agreement between nursing providers and nursing insurance aiming at comprehensive care, under the given circumstances cannot be executed satisfactorily. This is true especially for stage III patients in old people's homes.

Variations in end-expiratory pressure during partial liquid ventilation: impact on gas exchange, lung compliance, and end-expiratory lung volume.

STUDY OBJECTIVES: To determine the effects of different levels of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) on gas exchange, lung compliance, and end-expiratory lung volume (EELV). DESIGN: Prospective animal study. SETTING: Animal physiology research laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Animals underwent saline solution lavage to produce lung injury. Perflubron was instilled via the endotracheal tube in a volume estimated to represent functional residual capacity. The initial PEEP setting was 4 cm H(2)O, and stepwise changes in PEEP were made. At 30-min intervals, the PEEP was increased to 8, then 12, then decreased back down to 8, then 4 cm H(2)O. MEASUREMENTS AND RESULTS: After 30 min at each level of PEEP, arterial blood gases, aortic and central venous pressures, heart rates, dynamic lung compliance, and changes in EELV were recorded. Paired t tests with Bonferroni correction were used to evaluate the data. There were no differences in heart rate or mean BP at the different PEEP levels. CO(2) elimination and oxygenation improved directly with the PEEP level and mean airway pressure (Paw). Compliance did not change with increasing PEEP, but did increase when PEEP was lowered. EELV changes correlated directly with the level of PEEP. CONCLUSIONS: As previously reported during gas ventilation, oxygenation and CO(2) elimination vary directly with PEEP and proximal Paw during PLV. EELV also varies directly with PEEP. Dynamic lung compliance, however, improved only when PEEP was lowered, suggesting an alteration in the distribution of perflubron due to changes in pressure-volume relationships.

Randomized controlled trial of volume-targeted synchronized ventilation and conventional intermittent mandatory ventilation following initial exogenous surfactant therapy.

We set out to evaluate the impact of volume-targeted synchronized ventilation and conventional intermittent mandatory ventilation (IMV) on the early physiologic response to surfactant replacement therapy in neonates with respiratory distress syndrome (RDS). We hypothesized that volume-targeted, patient-triggered synchronized ventilation would stabilize minute ventilation at a lower respiratory rate than that seen during volume-targeted IMV, and that synchronization would improve oxygenation and decrease variation in measured tidal volume (V(t)). This was a prospective, randomized study of 30 hospitalized neonates with RDS. Infants were randomly assigned to volume-targeted ventilation using IMV (n = 10), synchronized IMV (SIMV; n = 10), or assist/control ventilation (A/C; n = 10) after meeting eligibility requirements and before initial surfactant treatment. Following measurements of arterial blood gases and cardiovascular and respiratory parameters, infants received surfactant. Infants were studied for 6 hr following surfactant treatment. Infants assigned to each mode of ventilation had similar birth weight, gestational age, and Apgar scores at birth, and similar oxygenation indices at randomization. Three patients were eliminated from final data analysis because of exclusionary conditions unknown at randomization. Oxygenation improved significantly following surfactant therapy in all groups by 1 hr after surfactant treatment (P < 0.05). No further improvements occurred with time. Total respiratory rate was lowest (P < 0.05) and variation in tidal volume (V(t)) was least in the A/C group (P < 0. 05). Minute ventilation (V(')(E)), delivered airway pressures, respiratory system mechanics, and hemodynamic parameters were similar in all groups. We conclude that volume-targeted A/C ventilation resulted in more consistent tidal volumes at lower total respiratory rates than IMV or SIMV. Oxygenation and lung mechanics were not altered by synchronization, possibly due to the volume-targeting strategy. Of the modes studied, A/C, a fully-synchronized mode, may be the most efficient method of mechanical ventilator support in neonates receiving surfactant for treatment of RDS.

Synchronized gas and partial liquid ventilation in lung-injured animals: improved gas exchange with decreased effort.

We hypothesized that partial liquid ventilation (PLV) with perflubron in spontaneously breathing lung-injured animals would increase respiratory workload compared to animals treated with gas ventilation (GV), and that a fully synchronized mode, assist-control ventilation (AC), would reduce the piglets' effort when compared to intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV) during both GV and PLV. Newborn piglets with saline lavage-induced lung injury were randomized to sequential 30-min periods of IMV --> SIMV --> AC (n = 5), or AC --> SIMV --> IMV (n = 5) during GV followed by PLV. Pulmonary mechanics measurements and an esophageal patient effort index (PEI, defined as the product of the area below baseline of the esophageal pressure-time curve and respiratory rate [RR]) were determined to estimate the patient's nonmechanical work of breathing, using a computer-assisted lung mechanics analyzer. GV to PLV comparisons showed no change in PEI (IMV, 57.8 vs. 49.7; SIMV, 52.3 vs. 46.8; AC, 15.7 vs. 13.7 cm H2O x s/min); intermode comparisons showed significantly decreased PEI in AC vs. IMV and SIMV during GV, and in AC vs. SIMV (AC vs. IMV, P = 0.06) during PLV. AC consistently resulted in the highest minute ventilation, lowest total respiratory rate, most physiologic pH, and least tidal volume variability. These observations suggest that synchronization with AC during GV and PLV may have substantial physiologic benefits.

Dynamics of spontaneous breathing during patient-triggered partial liquid ventilation.

This study evaluates different ventilator strategies during gas (GV) and partial liquid ventilation (PLV) in spontaneously breathing animals. We hypothesized that during PLV, spontaneously breathing animals would self-regulate respiratory parameters by increasing respiratory rate (RR) and minute ventilation (V'E) when compared to animals mechanically ventilated with gas, and further that full synchronization of each animal's effort to the ventilator cycle would decrease RR at stable tidal volumes (V(T)). We studied 12 newborn piglets (1.54 +/- 0.24 kg) undergoing GV and PLV in 3 different modes: intermittent mandatory ventilation (IMV), synchronized IMV (SIMV), and assist control ventilation (AC). Modes occurred sequentially in random order during GV first, with the same order then repeated during PLV. Animals initially received continuous positive airway pressure (CPAP) and returned to CPAP during PLV at the end of the experiment. Pressure-limited, volume-targeted ventilation was used with a tidal volume goal of 13 cc/kg. Rate was set at 10/min during IMV and SIMV, with a back-up rate of 10/min during AC. RR, V'E, mechanical (V(T)) and spontaneous tidal volumes (sV(T)) were measured breath-to-breath using a computer-assisted lung mechanics analyzer; mean values were determined over 30-min periods. Data analysis used paired t-tests with Bonferroni correction as needed (P < 0.05). Blood gases were stable in all modes during GV and PLV. RR (min(-1)) and V'E (L x min(-1)/kg) increased in all modes from GV to PLV (RR: CPAP 71 vs. 128; IMV 69 vs. 112; SIMV 65 vs. 107; AC 33 vs. 47. V'E: CPAP 0.47 vs. 0.72; IMV 0.46 vs. 0.61; SIMV 0.45 vs. 0.61; AC 0.38 vs. 0.53; P < 0.05). Intermode comparisons during PLV showed a lower RR with AC (P < 0.02), and a higher V'E with CPAP (P < 0.05). V(T) and dynamic respiratory system compliance decreased from GV to PLV (V(T) P < 0.05; C(rs,dyn) P < 0.01); sV(T) remained unchanged. V(T) and sV(T) did not differ in intermode comparisons. We conclude that during PLV, spontaneously breathing piglets with normal lungs maintain physiologic blood gases by increasing V'E through increased RR. AC produced the most efficient respiratory pattern during PLV, with increased V'E achieved by a modest increase in RR.

Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial.

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.

[Motor seizure patterns: a comparative analysis of tonic, psychomotor and psychogenic seizures]. / Motorische Anfallsschablonen: Eine vergleichende Analyse tonischer, psychomotorischer und psychogener Anfälle.

The motor patterns are self-regulating standardized movement models under normal and pathological conditions. Once learned and then automatized, they form the elements of the voluntary motor activity. Accordingly even the motor phenomena of epileptic seizures are defined as models or patterns. This paper is concerned with the question whether the epileptic patterns are to be associated to the neurophysiological regulatory processes of voluntary motoricity or whether these are pathological processes without relation to the physiological movement patterns. At the outset a short introduction to the neurophysiological basis of the voluntary motoricity is presented, which is built up according to the medullary organization of the cortex and taking into consideration the movement control through "feed forward" and "feed back". To the motor patterns of generalized tonic seizures connections to ontogenetic and phylogenetic old movement patterns and their activation through the epileptic excitation are denied. The tonic seizures are considered as pathological epileptic patterns, which are caused as a result of epileptic excitation, following their own dynamics. They represent a clear marking of maximum discharges of the cerebral structures, which control all other neuronal processes as well. The motor phenomena concerning the psychomotor seizures are described as specific patterns in respect of patients and types of seizures. To be differentiated are the elementary patterns of the first stage of seizures and the patterns of psychomotor twilight states. They represent denatured fragments of physiological motoricity and biological behavioural patterns. They would be brought in motion by the epileptic excitation, which in turn could lead to extensive motor phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

[Discontinuing anticonvulsant therapy: anthropologic aspects]. / Beendigung antiepileptischer Therapie: Anthropologische Aspekte.

The ultimate aim of a successful treatment of epilepsy is freedom from seizures, even after the discontinuation of medicinal treatment. Relapses can however not be excluded even under a favorable course of the disease. In the event of a good medical prognosis in respect of relapses, a recurrence of seizure can lead to a severe threat in the sphere of social and personal life of the individual. On the basis of specimen examples such situations in life are presented, wherein relapse of seizures resulted in serious psycho-social problems. From the unstable periods of life, special emphasis is placed on the second "social" phase of puberty. The complexity of situation in this period of life, together with its closely following transitory phases of one social structure into another (school, professional training, career) demands caution in planning the discontinuation of therapy, as relapses may lead to disturbing consequences on further plans of life. This applies even more to professional part of life, threatening the stability of employment with frequent change of jobs, resulting in a vulnerable area. The consequences of relapses can lead to regression of professional progress, the loss of external existence and lack of one's own self confidence. The significance of fear and anxiety as marked factors contributing for relapses will be emphasized. More over it is important to consider carefully the pathogenic family structure, in which relapse can break out concealed fears and rejections leading to serious disturbances in the private life of the subject. The discontinuation of antiepileptic medication under suitable circumstances is not basically disagreed upon.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function in prematures with respiratory distress syndrome (RDS).

Reports on thyroid function in newborns with respiratory distress syndrome (RDS) are controversial, the significance of obtained results is not clear. Therefore we conducted a longitudinal study of thyroid function in 35 infants with RDS (gestational age 24-36 weeks, birth weights 650-2770 g). 43 well prematures, matched for gestational age, served as controls. No significant differences were observed in cord blood TSH, T3, T4, TBG values and T4:TBG ratios between infants with and without RDS. Prematures with RDS showed lower levels of T3, T4, TBG and T4:TBG at 24 hours of age and increases of TSH values at 72 hours. Subsequently these prematures exhibited a spontaneous rise in thyroid hormone levels. Even non-surviving RDS-infants had initial T3, T4, T4:TBG and TSH values within the normal range. Thyroid hormone concentrations correlated significantly with the severity of pulmonary disease. Depressed thyroid hormone levels were found to be the result and not the cause of RDS. T4 or T3 therapy is not warranted in this condition.

Bioavailability of three phenytoin preparations in healthy subjects and in epileptics.

Serum phenytoin concentrations have been studied in epileptic patients and healthy subjects taking tablets of phenytoin calcium (Desitin), A, phenytoin acid (Desitin), B, and phenytoin acid (Nordmark), C. Retrospective data and prospective investigation of hospitalized patients on long-term phenytoin treatment showed that significantly higher serum concentrations of phenytoin were produced by the phenytoin acid preparations B and C than by the phenytoin calcium preparation A. In a cross over study six volunteers received 200 mg/day of preparations A, B, and C for three weeks. In this study, too, higher phenytoin serum concentrations were produced by B and C than by A, although the differences were not statistically significant. The reasons for the discrepancies between the studies in healthy and epileptic subjects are discussed.

[Enflurane anaesthesia for epileptic patients (author's transl)]. / Enfluran-Anaesthesien bei Epileptikern.

Enflurane anaesthesia with continuous EEG-registration was given to 21 patients, aged 3 to 53 years, who had a history of cerebral convulsions. 11 patients were children up to the age of 14 years. There was no obvious changes or correlation between enflurane concentration and intraoperative EEG-findings. The registered cramp potentials were the same as those registered preceeding the operations. Provocation as a result of the enflurane anaesthesia was not observed in any patient. The anticonvulsive basic treatment preceeding the operations made the interpretation of our results difficult. The warning by some authors against the use of Enflurane anaesthesia in patients with a history of cerebral convulsions could not be confirmed. Therefore, we conclude that a history of cerebral convulsions is not a general contraindication for the use of enflurane.