Characteristics of fatal penetrating injury; data from a retrospective cohort study in three urban regions in the Netherlands.

INTRODUCTION: Penetrating injury (PI) is a relatively rare mechanism of trauma in the Netherlands. Nevertheless, injuries can be severe with high morbidity and mortality rates. The aim of this study is to assess fatalities due to PI and evaluate the demographic parameters, mechanism of injury and the resulting injury patterns of this group of patients in three Dutch regions. METHODS: Patients suffering fatal PI (stab- and gunshot injuries), in the period between July 1st 2013 and July 1st 2019, in the region of Amsterdam, Utrecht and The Hague were included. Data were collected from the electronic registration system (Formatus) of the regional departments of Forensic Medicine. RESULTS: During the study period 283 patients died as the result of PI. The mean age was 44 years (SD 16.9), 83% was male and psychiatric history was reported in 22%. Over 60% of the injuries were due to assault and 35% was self-inflicted. Almost half of the incidents took place at home (47%). Injuries were most frequently to the head (24%) and chest (16%). Mortality was due to exsanguination (chest 27%, multiple body region's 17%, neck 9% and extremities 8%) and traumatic brain injury (21%). Up to 40% of the patients received medical treatment, surgical intervention was performed in 25%. The injuries to the extremities suggest a (potentially) preventable death rate of over 8%. Over 70% of the total population died at the scene. CONCLUSION: Fatal PI most often involves the relatively young, male, and psychiatric patient. Self-inflicted fatal PI accounted for 35%, addressing the importance of suicide prevention programs. Identification of preventable deaths needs more awareness to reduce the number of fatal PI.

Does peer consultation between forensic physicians reduce inter-doctor variation when issuing medical death certifications?

INTRODUCTION: Because earlier research showed that inaccuracies were observed in the interpretation and handling of deaths by forensic physicians, peer consultation among forensic physicians was introduced before advice was given to treating physicians calling for advice. In addition, peer consultation was introduced as a means to improve the correctness of conclusions concerning the manner of death when performing external post-mortem examinations. METHOD: In the period of November 2017 until April 2018 all reports of external postmortem examinations (n = 498) and all telephonic consultations between treating physicians with forensic physicians, concerning postmortem examinations (n = 167), were analyzed retrospectively. RESULTS: Peer consultation among forensic physicians took place in 70% of the 167 telephonic consultations initiated by treating physicians. In 92% of all cases of telephonic consultation, the accurateness of advice to treating physicians was deemed accurate. In 67% (n = 498) of all external postmortem examinations in the study period, peer consultation between forensic physicians took place. The conclusion regarding the manner of death after external postmortem examination was accurate in 99% of all cases (n = 491 out of 498). CONCLUSION: The advices given by forensic physicians to treating physicians have improved after the introduction of peer consultation among forensic physicians. Peer consultation therefore should be recommended as a means for quality assurance.

[Exchange of information between psychiatrist and pharmacist concerning uncollected medication]. / Informatie-uitwisseling tussen psychiater en apotheker over niet-opgehaalde medicatie.

Background Non- compliance with drug regimens has a negative effect on symptomatology and is the largest predictor of relapse in people with Severe Psychiatric Disorder (EPA). When care providers are informed in good time that medication has not been collected and can act on it, compliance can be increased. Aim Assessment of usefulness and feasibility of a system for the Signaling and Reporting by Pharmacists of Uncollected Medication for people with an EPA (Dutch: 'SMANOM-EPA') within the current legal context. Method The package of requirements was drawn up on the basis of questionnaires and telephone interviews with psychiatrists and pharmacists and focus group meetings with patients and significant others. Lawyers and ICT professionals were consulted to formulate the legal and technical preconditions. Results All parties involved considered SMANOM-EPA to be useful. The administrative burden was a determining factor for the feasibility and transparency was an important precondition. The exchange of information could take place securely with existing technology, despite the variation in prescribing and issuing systems. However, opinions were divided as to whether informing and documenting is sufficient or whether consent is necessary. Conclusion The GDPR and the WBGO safeguard patients' rights regarding the use of personal data. Uncertainty about the legal framework and technological possibilities add to the complexity of innovations to promote the exchange of information between practitioners, while the added value is seen by those involved and in comparable innovations. Tijdschrift voor Psychiatrie 63(2021)1, 32-38.

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.

Hospital referral of detainees during police custody in Amsterdam, The Netherlands.

This study describes how many detainees have been referred to emergency departments for further evaluation or emergency care while in police custody in Amsterdam (years 2012/2013). It provides insights into the diagnoses assigned by forensic doctors and hospital specialists and the appropriateness of the referrals. We made use of the electronic registration system of the Forensic Medicine Department of the Public Health Service Amsterdam. This department is in charge of the medical care for detainees in the Amsterdam region. Hospital diagnoses were obtained through collaboration with several Amsterdam-based hospitals. According to our results, in 1.5% of all consultations performed, the detainee was referred to hospital. The most frequent reasons for referral were injuries (66%), intoxication/withdrawal (11%) and cardiac problems (7%). In 18% of all referrals, hospital admission (defined as at least one night in the hospital) was the consequence. After review of hospital files, the indication for referral as stated by the forensic physician was confirmed in 77% of all cases. A minority of referrals was considered unnecessary (7%). The identified cases allow for a discussion of cases of over-referral. Future research should focus on the problem of under-referral and associated health risks.

Calling for advice: Aspects of telephonic consultation in post-mortem examinations.

INTRODUCTION: Research on telephonic consultation in forensic medicine is scarce. This study aimed to create insight in different aspects of telephonic consultation in post-mortem examinations. Besides, the accuracy of advice given by forensic physicians and associations between accuracy and characteristics of forensic physicians were evaluated. METHODS: A descriptive, retrospective study was conducted. Data were obtained from the electronic information system used by the department of forensic medicine in Amsterdam. Cases in which telephonic advice was given, with regard to post-mortem examinations, were identified and the accuracy of advice was appraised. Questionnaires were distributed among forensic physicians in order to obtain information about characteristics of physicians. Hence, associations of these characteristics and accuracy of advice were to be revealed. RESULTS: A total of 938 cases were included. Telephonic advice was most often requested by hospitals (n = 359, 38.3%), followed by general practices (n = 273, 29.1%) and nursing homes (n = 144, 15.4%). Incorrect advice was given significantly more often in cases regarding manner of death compared to other categories of consultation (n = 104 of 110, 94.5%, p < 0.001). Among the forensic physicians, 27.3% (six out of 22) were responsible for 60.9% (67 out of 110 cases) of the cases wherein incorrect advice was given. After correction for dependency of observations, no associations were found between characteristics of physicians or time of consultation and accuracy of advice. CONCLUSION: This study indicates that education concerning post-mortem external examinations is needed for both consulting parties as well as forensic physicians.

Altered hip muscle forces during gait in people with patellofemoral osteoarthritis.

OBJECTIVES: The study aimed to (1) assess whether higher vasti (VASTI), gluteus medius (GMED), gluteus maximus (GMAX) and gluteus minimus (GMIN) forces are associated with participant characteristics (lower age, male gender) and clinical characteristics (lower radiographic disease severity, lower symptom severity and higher walking speed); and (2) determine whether hip and knee muscle forces are lower in people with patellofemoral joint (PFJ) osteoarthritis (OA) compared to those without PFJ OA. DESIGN: Sixty participants with PFJ OA and 18 (asymptomatic, no radiographic OA) controls ≥40 years were recruited from the community or via referrals. A three-dimensional musculoskeletal model was used in conjunction with optimisation theory to calculate lower-limb muscle forces during walking. Associations of peak muscle forces with participant and clinical characteristics were conducted using Pearson's r or independent t-tests and between-group comparisons of mean peak muscle forces performed with walking speed as a covariate. RESULTS: Peak muscle forces were not significantly associated with participant, symptomatic or radiographic-specific characteristics. Faster walking speed was associated with higher VASTI muscle force in the PFJ OA (r = 0.495; P < 0.001) and control groups (r = 0.727; P = 0.001) and higher GMAX muscle force (r = 0.593; P = 0.009) in the control group only. Individuals with PFJ OA (N = 60) walked with lower GMED and GMIN muscle forces than controls (N = 18): GMED, mean difference 0.15 [95% confidence interval (CI): 0.01 to 0.29] body weight (BW); GMIN, 0.03 [0.01 to 0.06] BW. No between-group differences were observed in VASTI or GMAX muscle force: VASTI, 0.10 [-0.11 to 0.31] BW; GMAX, 0.01 [-0.11 to 0.09] BW. CONCLUSION: Individuals with PFJ OA ambulate with lower peak hip abductor muscle forces than their healthy counterparts.

Prevalence and incidence of endocrine disorders in children: results of a survey in Baden-Wuerttemberg and Bavaria (EndoPrIn BB) 2000-2001.

BACKGROUND: Sparse data is available on the incidence of endocrine disorders among children in Germany. AIM: A pioneer study was established to analyse, in the German states of Baden-Wuerttemberg (BW) and Bavaria (BY), the incidence and prevalence of congenital adrenal hyperplasia (AGS; CAH), precocious puberty (PP), primary congenital hypothyreosis (PCH), Graves disease (MB), and growth disorders related to the Ullrich-Turner syndrome (UTS) and growth hormone deficiency (GHD). METHODS: Participation in the study involved each paediatric hospital in BW and BY (n = 63),and all regional paediatricians belonging to the Association of Statutory Health Insurance Physicians (SHI) practising in these states (n = 1 443). Data collection was done from January 1, 2000, to December 31, 2001, and included all patients in the 0- < 18 age range. RESULTS: Completeness of data was 81 % for CAH and 55 % for UTS (capture-mark-recapture method).The incidence rate (IR, per 100 000 / year)versus prevalence rate (per 100 000 at the time point December 31, 2001) was: CAH 0.64 vs.9.60; PP 2.42 vs. 10,85; PCH 1.88 vs. 14.97; MB 0.89 vs. 3.25; UTS 2.15 vs. 29.07; and GHD 3.47(IR). Among neonates, the incidence of CAH was 1 / 7 794; PCH 1 / 2 629 and UTS 1 / 2 300. CONCLUSIONS: A pioneer study has been established in Germany for investigating the frequency of AGS (CAH), PP, PCH, MB, UTS, and GHD among children and adolescents. Our data shows that these disorders occur in approx. 2,700 children per year in total Germany, and about 12 000 of these children need to be treated in specialized paediatric endocrinological centres.

Prospective cohort study into post-disaster benzodiazepine use demonstrated only short-term increase.

OBJECTIVES: Benzodiazepines are typically prescribed for anxiety and insomnia, two complaints often reported after disasters. Benzodiazepines can cause mental or physical dependence, especially when taken for a long time. This study aims at evaluating benzodiazepine use in a disaster-stricken community with the help of computer-based records. STUDY DESIGN AND SETTING: This prospective cohort study covers a period of 4 years. For every patient, predisaster baseline data are available. Multilevel regression is applied to study differences in benzodiazepine use in 496 patients whose children were involved in the Volendam café fire on January 1, 2001 compared with 1,709 community controls, and 4,530 patients from an unaffected cohort. RESULTS: In community controls and patients from the unaffected cohort, benzodiazepine use remained stable in the course of the years. In the first year postfire, parents of disaster victims were 1.58 times more likely to use benzodiazepines than community controls (95% confidence interval 1.13-2.23). With regard to long-term use, differences between community controls and parents were statistically nonsignificant. CONCLUSIONS: In the studied community, benzodiazepines were predominantly prescribed as a short-term intervention. Clinical guidelines that advocate a conservative prescription policy were well adhered to.

Germline and mosaic mutations of FLN1 in men with periventricular heterotopia.

OBJECTIVE: To describe the phenotypic spectrum and genetics of periventricular nodular heterotopia (PNH) caused by FLN1 mutations in four men. BACKGROUND: X-linked PNH caused by FLN1 mutations (MIM #300049) implies prenatal or early postnatal lethality in boys and 50% recurrence risk in daughters of affected women. METHODS: Clinical examination, cognitive testing, MRI, and mutation analysis (denaturing high-performance liquid chromatography and direct sequencing) on blood lymphocytes and single hair roots were performed for nine affected individuals, including three men. Neuropathologic study of the brain was performed for an affected boy. RESULTS: In two families, missense mutations were transmitted from mother to son (Met102Val) and from father to daughter (Ser149Phe), causing mild phenotypes in both genders, including unilateral PNH. In a third family, a man was mosaic for an A>G substitution (intron 11 acceptor splice site) on leukocyte DNA and hair roots (mutant = 42% and 69%). Single hair root analysis confirmed that the mutation was not present in all ectodermal derivative cells. A healthy daughter had inherited the X chromosome from her father's wild-type germinal cell population. In the fourth family, an eight-base deletion (AGGAGGTG, intron 25 donor splice site) led to early deaths of boys. Postmortem study in a newborn boy revealed PNH and cardiovascular, genitourinary, and gut malformations. CONCLUSIONS: Periventricular nodular heterotopia caused by FLN1 mutations in men has a wide clinical spectrum and is caused by different genetic mechanisms, including somatic mosaicism. Mutation analysis of FLN1 should support genetic counseling in men with periventricular nodular heterotopia.

Epilepsy and trisomy 19q--different seizure patterns in a brother and a sister.

In symptomatic epilepsies due to chromosomal aberrations, epileptogenesis may be either the direct consequence of deletion or duplication of a gene causing seizures or may have a more complex etiology caused by the disturbance of the interaction of several genes and environmental factors. We report on a brother and a sister with trisomy 19q13.3-->qter who present different epileptologic features and discuss epileptogenesis in this syndrome with respect to genes known to be located on the distal part of chromosome 19q. Both patients share mental retardation and several dysmorphic features. The boy was hypoxic at birth and showed an extremely delayed psychomotor development. The girl, however, had no significant neonatal problems, and her psychomotor development was better. Although the male had an abnormal EEG in childhood, his first partial seizures occurred only as late as at age 31 years. He subsequently became seizure-free with carbamazepine (CBZ). In contrast, the girl already suffered from absence-like seizures during childhood and became seizure-free under ethosuccimide (ESM). A photoparoxysmal response, however, is still visible in her EEG. The difference between the epileptologic features in these siblings points to epileptogenic mechanisms placed far downstream on the way from genotype to phenotype. The photoparoxysmal response--otherwise a facultative finding in genetically determined epilepsies--in the EEG of the sister, however, points to a closer relationship between the duplicated genes and epileptogenesis. The fact that genes encoding potassium channels are located on 19q13.3-q13.4 may also support the latter assumption.

Assault by burning--a retrospective review with focus on legal outcomes.

A small but significant number of adults admitted to our burn center were assaulted by burning. Eighty-five such cases were identified at our burn center. Fifteen deaths were caused by these assaults. These cases are in one sense unique in that in addition to the burn victim, society is also obliged to expend resources dealing with the assailant.

[Dostoievsky's life in the interrelation between epilepsy and literature]. / Dostojewskijs Leben im Wechselspiel zwischen Epilepsie und Literatur.

Fyodor Mihailovich Dostoievsky is considered one of the most important Russian authors of the nineteenth century. He suffered from epilepsy since childhood, which disease often was a theme in his novels. This paper describes Dostoievsky's life and examines the various epileptic protagonists appearing in his works. Finally, the author's own epilepsy and particularly its etiology are discussed.

[Epilepsy. Classification and genetics]. / Epilepsien. Klassifikation und Genetik.

A common symptom of epilepsies are recurrent unprovoked epileptic seizures. These can be classified as focal or generalised. Thus, we can speak of focal or generalised epilepsies. Considering the rest of the medical history and the results of EEG and brain imaging the terms idiopathic, symptomatic and cryptogenic (i.e. probably symptomatic) are used to further characterise an epilepsy in a single patient. These classification scheme which is used since the end of the eighties allows decision making in therapy and an estimation of prognosis. Due to progress in epileptology during the last decade a more sophisticated approach is required. Thus, semiology of the single seizure becomes more important. The evolution of signs and symptoms during a seizure tells us something about the seizure onset zone and the mode of seizure propagation. The knowledge of them is a prerequisite for surgical treatment. Furthermore, semiology of seizures should determine social implications of epilepsy by far more than the fact that they are epileptic. Beside seizure semiology we have to consider the underlying neuropathological condition since it determines treatment and prognosis. Epilepsy is a consequence of acquired or genetic brain diseases. In case of the latter it becomes more and more possible to characterise and diagnose the genetic syndromes and to understand their pathophysiology. In epileptology the exact knowledge of an underlying genetic disease is not only of scientific interest. Beside being a condition sine qua non for adequate genetic counselling it influences the choice of anti-epileptic drugs and determines whether surgical treatment is indicated. Thus genetics are an important part of comprehensive care in epilepsy.

Time course of motion adaptation: motion-onset visual evoked potentials and subjective estimates.

The aim of this study was to quantitatively describe the dynamics of adaptation to visual motion with electrophysiological and psychophysical methods in man. We recorded visual evoked potentials (VEPs) to motion onset of random dot patterns from occipital and occipito-temporal electrodes during a succession of adaptation-recovery sequences. In these sequences the test stimulus was used to set the adaptation level: seven trials with 70% motion duty cycle (adaptation) followed by seven trials of 7% motion duty cycle (recovery). In a similar paradigm we determined the length of the perceptual motion after-effect to obtain a psychophysical measure of the time course of motion adaptation. Our results show a highly significant reduction of the N2 amplitude in the maximally compared to the minimally adapted condition (P < 0.001). Electrophysiological and psychophysical results both indicate that adaptation to visual motion is faster than recovery: The data were fit with an exponential model yielding adaptation and recovery time constants, respectively, of 2.5 and 10.2 s for the N2 amplitude (occipito temporal derivation) and of 7.7 and 16.7 s for the perceptual motion after-effect. Implications for the design of motion stimuli are discussed, e.g. a motion stimulus moving 10% of the time may lead to about 30% motion adaptation.

Regional hypometabolism in an acute model of focal epileptic activity in the rat.

Focal epileptic activity can be expected to influence distant brain areas via far reaching connections. To investigate such interactions the effects of focal epileptic activity on the metabolism of the brain were investigated in the rat cortex. Focal epileptic activity was induced by the application of penicillin onto the motor cortex. The focus, and to a lesser extent homotopic contralateral brain areas, showed an increase in the regional cerebral metabolic rate of glucose (rCMRGlc) as measured by [14C]deoxyglucose autoradiography. This focal hypermetabolism was accompanied by widespread hypometabolism lateral to the focus. The decrease of rCMRGlc occurred in somatosensory cortical areas but not in the motor cortex behind or in front of the focus, the perirhinal cortex or the occipital cortex. It was associated with an increase in metabolic rate in the ventrolateral, ventroposteromedial, ventroposterolateral and, in particular, posterior nuclei of the thalamus. It is hypothesized that the widespread reduction of rCMRGlc in the somatosensory cortical areas is due to inhibition via thalamic nuclei caused by activity in the motor cortex.

Refractory periods following interictal spikes in acute experimentally induced epileptic foci.

Under epileptic conditions, interictal epileptic events are followed by large inhibitions which prevent the transition to ictal discharges. In the present experiments the refractory period following interictal epileptic spikes was investigated in animal experiments. Interictal epileptic activity was elicited by application of penicillin onto the motor cortex of anesthetized rats. Interictal epileptic discharges were followed by an absolute refractory phase lasting 200-300 msec, in which no epileptic event could be elicited by epicortical stimulation. This was followed by a relative refractory period up to 900 msec after onset of the conditioning spike; spikes elicited with intervals between 300 and 900 msec were smaller than those with greater intervals and required higher stimulation intensities. This period ends by a sharp drop of threshold. In two-thirds of the experiments, spikes were favoured in intervals of 300-500 msec due to a sag of the threshold, which possibly indicates recurrent neuronal excitations. Stimulations with frequencies of about 1/sec favoured a transition from a pattern with spikes appearing in an irregular sequence every 2-3 sec, to a discharge pattern with spikes appearing with regular intervals of about 1 sec. This change of firing pattern was associated with a drop of the spike threshold. It is concluded that interictal epileptic events are followed by a refractory period comprising different components. Alterations of the neuronal inhibitions responsible for these refractory phases may be critical for the activity of the focus and may determine the transition from interictal to ictal discharges.

Service delivery patterns for adults with mild mental retardation at community mental health centers.

Results of a national survey on mental health services for adults with mild mental retardation sent to directors of psychological services at community mental health centers was discussed. In general, adults with mild mental retardation were less likely to receive the full array of available services. Individuals with mental retardation were not frequent consumers of community mental health services and received differential treatment at these Centers. Implications of these findings were discussed.