Real-world reported adverse events related to systemic immunomodulating therapy in patients with atopic dermatitis: Results from the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

BACKGROUND: Evidence on the (long-term) safety of systemic immunomodulating therapies in atopic dermatitis (AD) generated by real-world data is sparse. OBJECTIVES: To describe real-world reported adverse drug reactions (AEs) related to systemic immunomodulating therapy in patients with AD and to compare the incidence rates of AEs with the Summaries of Product Characteristics (SmPCs). METHODS: We conducted an observational prospective multi-centre cohort study, using the TREAT NL registry. All severe AEs, AEs of special interest and serious AEs in adult and paediatric patients on systemic immunomodulating treatment (ciclosporin, methotrexate, azathioprine, mycophenolic acid, dupilumab, tralokinumab, baricitinib and upadacitinib) were assessed. Incidences rates of all (potentially) drug-related AEs were standardized in patient years and compared to the cumulative incidences in the associated SmPCs. RESULTS: We collected 422 patient years of safety data from 266 patients, of whom 129 (48.5%) reported a total of 224 (potentially) drug-related AEs. Compared to dupilumab's SmPC, higher incidence rates were found for four AEs (reported ≥5 times): eosinophilia, blepharitis, dry eyes and head and neck erythema (i.e. dupilumab facial redness). A higher incidence rate of fatigue was found in patients on oral methotrexate in our cohort compared to the SmPC. Two new drug-related AEs (reported ≥5 times) were found in patients on dupilumab, including non-infectious conjunctivitis and meibomian gland dysfunction. CONCLUSIONS: Real-world reported AEs captured in AD patient registries can add information on the estimated incidence of AEs and benefit clinical decision aids. Future studies using data derived from the TREAT NL registry combined with data from other registries within the TREAT Registry Taskforce will provide more information on (rare) AEs associated with immunomodulating therapy in AD patients.

Lentigo maligna (melanoma): A systematic review and meta-analysis on surgical techniques and presurgical mapping by reflectance confocal microscopy.

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n = 1355), staged excision (n = 2442) and Mohs' micrographic surgery (MMS) (n = 2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes.

The European TREatment of ATopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate-to-severe atopic eczema.

BACKGROUND: For many years dermatologists have had access to few therapies for patients with moderate-to-severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well-known safety profiles, lower costs and wider availability. OBJECTIVES: To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice. METHODS: In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use. RESULTS: From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience. CONCLUSIONS: This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off-label therapies are also preferred as first-line choice of systemic therapy.

Novel endotypes in heart failure: effects on guideline-directed medical therapy.

Aims: We sought to determine subtypes of patients with heart failure (HF) with a distinct clinical profile and treatment response, using a wide range of biomarkers from various pathophysiological domains. Methods and results: We performed unsupervised cluster analysis using 92 established cardiovascular biomarkers to identify mutually exclusive subgroups (endotypes) of 1802 patients with HF and reduced ejection fraction (HFrEF) from the BIOSTAT-CHF project. We validated our findings in an independent cohort of 813 patients. Based on their biomarker profile, six endotypes were identified. Patients with endotype 1 were youngest, less symptomatic, had the lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and lowest risk for all-cause mortality or hospitalization for HF. Patients with endotype 4 had more severe symptoms and signs of HF, higher NT-proBNP levels and were at highest risk for all-cause mortality or hospitalization for HF [hazard ratio (HR) 1.4; 95% confidence interval (CI) 1.1-1.8]. Patients with endotypes 2, 3, and 5 were better uptitrated to target doses of beta-blockers (P < 0.02 for all). In contrast to other endotypes, patients with endotype 5 derived no potential survival benefit from uptitration of angiotensin-converting enzyme-inhibitor/angiotensin-II receptor blocker and beta-blockers (Pinteraction <0.001). Patients with endotype 2 (HR 1.29; 95% CI 1.10-1.42) experienced possible harm from uptitration of beta-blockers in contrast to patients with endotype 4 and 6 that experienced benefit (Pinteraction for all <0.001). Results were strikingly similar in the independent validation cohort. Conclusion: Using unsupervised cluster analysis, solely based on biomarker profiles, six distinct endotypes were identified with remarkable differences in characteristics, clinical outcome, and response to uptitration of guideline directed medical therapy.

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

INTRODUCTION: Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. METHODS AND RESULTS: BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). CONCLUSION: Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.

Hallmarks of cancer in patients with heart failure: data from BIOSTAT-CHF.

BACKGROUND: Within cardio-oncology, emerging epidemiologic studies have demonstrated a bi-directional relationship between heart failure (HF) and cancer. In the current study, we aimed to further explore this relationship and investigate the underlying pathophysiological pathways that connect these two disease entities. METHODS: We conducted a post-hoc analysis in which we identified 24 Gene Ontology (GO) processes associated with the hallmarks of cancer based on 92 biomarkers in 1960 patients with HF. We performed Spearman's correlations and Cox-regression analyses to evaluate associations with HF biomarkers, severity and all-cause mortality. RESULTS: Out of a total of 24 GO processes, 9 biological processes were significantly associated with adverse clinical outcome. Positive regulation of mononuclear cell proliferation demonstrated the highest hazard for reaching the clinical endpoint, even after adjusting for confounders: all-cause mortality HR 2.00 (95% CI 1.17-3.42), p = 0.012. In contrast, negative regulation of apoptotic process was consistently associated with a lower hazard of reaching the clinical outcome, even after adjusting for confounders: all-cause mortality HR 0.74 (95% CI 0.59-0.95), p = 0.016. All processes significantly correlated with HF biomarkers, renal function and HF severity. CONCLUSIONS: In patients with HF, GO processes associated with hallmarks of cancer are associated with HF biomarkers, severity and all-cause mortality.

Effect of selective dorsal rhizotomy on gait in children with bilateral spastic paresis: kinematic and EMG-pattern changes.

INTRODUCTION: Selective dorsal rhizotomy (SDR) is an effective treatment for reducing spasticity and improving gait in children with spastic cerebral palsy. Data concerning muscle activity changes after SDR treatment are limited. PATIENTS AND METHODS: In 30 children who underwent SDR a gait analysis was performed before and 12-24 months postoperatively. Subjects walked on a 10-m walkway at comfortable walking speed. Biplanar video was registered and surface EMG was recorded. Sagittal knee angles were measured from video and observational gait assessments were performed using the Edinburgh gait assessment scale (EGAS). RESULTS: The EGAS significantly improved after SDR (p<0.001). There were significant improvements of the knee angle kinematics (p<0.001). Only slight changes in EMG activity were observed. The activity of the m. gastrocnemius (GM) decreased and a late peak appeared in stance, the activity of the m. semitendinosus (ST) increased in stance. The activity of the m. rectus femoris (RF) decreased in swing. CONCLUSION: SDR improved overall gait performance but EMG changes were only slight. Better timing of the GM in stance and reduced activity of RF in swing may have increased knee flexion in swing. Reduced hamstrings spasticity may have led to postural instability in the hip.

Surgical morbidity and mortality of pediatric brain tumors: a single center audit.

OBJECTIVES: The primary aim of this study is to perform an internal quality control of pediatric brain tumor surgery in the neurosurgical department of the VU University Medical Center Amsterdam (The Netherlands). Secondly, this study aims to contribute to the accumulating data concerning outcome in pediatric neurosurgery, in order to establish institutional practice benchmarks. METHODS: We report the surgical mortality and morbidity of 121 patients (0-18 years) surgically treated for a brain tumor from January 1999 to August 2007. Patients, in whom only a brain tumor biopsy was performed, were excluded. RESULTS: Mean age at first surgery was 8.2 years. Of the 121 patients, 14 had a second surgery, and two underwent a third surgery (for a total of 137 operations). Of all 121 primary surgeries, 66% were total resections, 26% subtotal resections, and 8% partial resections. The overall surgical morbidity rate in this study was 69% after first surgery, 50% after second surgery, and one out of two after third surgery. CONCLUSION: These overall morbidity rates are comparable to other published mixed case series. The surgical mortality rate was 0.8%; this is comparable to the lowest rates reported for high-volume neurosurgical centers. We encourage other neurosurgical centers to collect, analyze, and publish their data. These data can then serve as a basis for comparison with other pediatric neurosurgical centers and will eventually lead to an improvement of pediatric neurosurgical practice and patient care.

What influences contracture formation in lower motor neuron disorders, severity of denervation or residual muscle function? An analysis of the elbow contracture in 100 children with unilateral Brachial Plexus Birth Injury.

PURPOSE: As in other neuromuscular disorders, both denervation and muscle paresis/imbalance are implicated as aetiological factors for contractures in children with a Brachial Plexus Birth Injury (BPBI). Although both factors are related, it is unclear which factor is dominant. The aim of this study is to assess whether contracture formation in children is predominantly related to denervation or to residual muscle function/imbalance. This might be relevant for understanding contracture formation in other neuromuscular disorders. METHODS: A total of 100 children (61 boys; mean age 10.4 years, 4 to 18) with unilateral BPBI were included in this cross-sectional study. Severity of the denervation was classified according to Narakas. Muscle function of flexors and extensors of both elbows was measured (in Newtons) using a hand-held dynamometer and flexion contractures were measured with a goniometer. The relation between denervation, muscle function/muscle balance and flexion contracture was assessed using univariate and multivariate analysis. RESULTS: Of the children, 57 were Narakas class I, 13 class II and 30 class III. Mean flexion contracture was 25° (90° to -5°). At the affected side the forearm flexion force was 47% and extension force was 67% of the force of the unaffected side. Contractures were more severe in children with higher Narakas classifications (p = 0.001), after neurosurgery (Mann-Whitney U test, p = 0.009) and were related to age (Spearman's Rho = -0.3, p = 0.008) and to paresis of the extensors (Rho = 0.4, p = 0.000). Flexor paresis as a percentage of unaffected side (Rho = 0.06, p = 0.6) and muscle balance had no influence. CONCLUSION: In BPBI, elbow contractures are related to the severity of the neurological lesion, not to residual muscle function. LEVEL OF EVIDENCE: Level II - prognostic study.

Effect of selective dorsal rhizotomy on daily care and comfort in non-walking children and adolescents with severe spasticity.

BACKGROUND: In non-walking children with severe spasticity, daily care can be difficult and many patients suffer from pain. Selective dorsal rhizotomy (SDR) reduces spasticity in the legs, and therefore has the potential to improve daily care and comfort. AIM: To examine effects of SDR on daily care and comfort in non-walking children with severe spasticity due to different underlying neurological conditions. METHODS: Medical history, changes in daily care and comfort and satisfaction with outcome were assessed retrospectively in non-walking children who underwent SDR in our center, with a mean follow-up of 1y 7m (range 11m-4y 3m). All eligible patients (n = 24, years 2009-2014) were included. RESULTS: Mean age at SDR was 12y 4m (SD 4y 3m, range 2y 8m-19y 3m). Associated orthopaedic problems were frequent. Seven patients underwent scoliosis correction in the same session. Most improvements were reported in dressing (n = 16), washing (n = 12) and comfort (n = 10). Median score for satisfaction was 7 on a scale of 10 (range 1-9). SDR resulted in reduction of spasticity in leg muscles. In nine patients dystonia was recorded post-operatively, mainly in children with congenital malformations and syndromes. INTERPRETATION: SDR is a single event intervention that can improve daily care and comfort in non-walking children with severe spasticity, and can safely be combined with scoliosis correction. Despite the improvements, satisfaction is variable. Careful attention is necessary for risk factors for dystonia, which may be unmasked after SDR.

Influence of transdermal scopolamine on motion sickness during 7 days' exposure to heavy seas.

We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty-nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects.

Retroversion of the humeral head in children with an obstetric brachial plexus lesion.

We undertook a prospective MRI study to measure the retroversion of the humeral head in 33 consecutive infants with a mean age of 1 year 10 months (3 months to 7 years 4 months) who had an obstetric brachial plexus lesion (OBPL). According to a standardised MRI protocol both shoulders and humeral condyles were examined and the shape of the glenoid and humeral retroversion determined. The mean humeral retroversion of the affected shoulder was significantly increased compared with the normal contralateral side (-28.4 +/- 12.5 degrees v -21.5 +/- 15.1 degrees, p = 0.02). This increase was found only in the children over the age of 12 months. In this group humeral retroversion was -29.9 +/- 12.9 degrees compared with -19.6 +/- 15.6 degrees in the normal shoulder (p = 0.009), giving a mean difference of 10.3 degrees (95% confidence interval 3.3 to 17.3). This finding is of importance when considering the operative treatment for subluxation of the shoulder in children with an OBPL.

Deformities of the shoulder in infants younger than 12 months with an obstetric lesion of the brachial plexus.

We performed a prospective study using MRI in 16 consecutive infants with a mean age of 5.2 months (2.7 to 8.7) who had shown inadequate recovery from an obstetric lesion of the brachial plexus in the first three months of life, in order to identify early secondary deformities of the shoulder. Shoulders were analysed according to a standardised MRI protocol. Measurements were made of the appearance of the glenoid, glenoid version and the position of the humeral head. The appearance of the glenoid on the affected side was normal in only seven shoulders. In the remainder it was convex in seven and bioconcave in three. The degree of subluxation of the humeral head was significantly greater (p = 0.01) in the affected shoulders than in normal shoulders (157 degrees v 170 degrees). The presence of an abnormal appearance of the glenoid, retroversion of the glenoid and subluxation of the humeral head increased with age. There was a statistical difference (p = 0.05) between infants younger than five months and those who were older.

Secondary deformities of the shoulder in infants with an obstetrical brachial plexus lesions considered for neurosurgical treatment.

OBJECT: The authors performed a prospective study in which magnetic resonance (MR) imaging was conducted in 26 consecutive infants (mean age 5.6 months, range 2.7-14.5 months) in whom recovery from an obstetric lesion of the brachial plexus had been inadequate in the first 3 months of life. The purpose was to identify early secondary deformations of the shoulder in obstetrical brachial plexus lesions (OBPLs). METHODS: Features of the shoulders were analyzed according to a standardized MR imaging protocol in patients with OBPLs. Measurements were made of the appearance of the glenoid, glenoid version, and the position of the humeral head. The appearance of the glenoid on the affected side was normal in only 11 shoulders. In the remainder it was convex in eight and biconcave in seven cases. The degree of humeral head subluxation was significantly greater (p = 0.001) in affected shoulders than in normal shoulders (152 and 170 degrees, respectively). The presence of abnormal glenoid retroversion and humeral head subluxation increased with age: there was a statistical difference (p = 0.001) between infants younger than 5 months of age and those who were older. CONCLUSIONS: Magnetic resonance imaging demonstrates shoulder-related anatomical and nerve root lesion, allowing evaluation of neural, osseous, and cartilaginous structures in younger children.

[Cerebellar abscess caused by an occipital dermal sinus in an infant]. / Cerebellair abces door een occipitale dermale sinus bij een zuigeling.

A 7.5-month-old girl was admitted with the clinical signs and symptoms of raised intracranial pressure. This was caused by an obstructive hydrocephalus, due to cerebellar abscesses induced by an infected contiguous complete occipital dermal sinus. Staphylococcus aureus was cultured. The patient was treated by radical excision of the dermal sinus and the abscesses after initial external drainage of the lateral cerebral ventricle, followed by systemic antibiotic therapy. The different types of dermoid cysts of the posterior cranial fossa are described. Early detection of congenital dermal abnormalities along the craniospinal axis by routine examination of newborns is prognostically important. Computerised tomography or magnetic resonance imaging are the methods of choice for further investigation of suspect dermal lesions.

[Vomiting as a first neurological sign of brain tumors in children]. / Braken als eerste neurologische symptoom van een hersentumor op de kinderleeftijd.

Four children (two boys aged 1.5 and 10 years and two girls aged 2 and 9 years) vomited for one-half to four weeks. In one child, ataxia was later also noted and another tilted his head constantly to the left, but this was initially not alarming. In all four cases CT revealed a brain tumour, for which they were operated. Postoperatively, one child had residual tumour tissue that caused no further problems, in two children the tumour was completely excised with no further symptoms and no recurrence in the following 2 years, and in one child complete excision was not possible so that chemotherapy and radiotherapy were given, but metastases nevertheless developed 10 months later and the child died. Vomiting is common in children and in most cases the result of infectious or gastrointestinal causes. Intracranial pathology also can cause vomiting, both by increased intracranial pressure and by direct stimulation of the vomiting centre in the brainstem. Brain tumours in children often lack specific neurological signs in their clinical presentation. Intractable or chronic vomiting without nausea or deregulation of the water and electrolyte balance could therefore indicate the presence of an intracranial process, even when other neurological signs are absent.

[Children with stumbling gait due to acute spinal cord compression]. / Kinderen met een wankel looppatroon door acute ruggenmergcompressie.

Three previously healthy children, two girls aged 2 and almost 5 years and a boy aged 20 months, developed a progressively stumbling gait within days. In two this occurred after a period of weeks during which they complained of, or seemed to have back pain. In all three cases acute spinal cord compression by a malignant tumour was diagnosed. Histological examination revealed Ewing sarcoma, granulocytic sarcoma and T-cell lymphoma. Surgical decompression led to complete neurological recovery. Although rare, acute spinal cord compression during childhood is a medical emergency because of the risk of neurological morbidity. Back pain, weakness and a stumbling gait usually are the first symptoms. Sensory symptoms and sphincter dysfunction may develop later. Early recognition is essential, as prognosis depends on neurological findings and duration of symptoms when treatment is started.

[Integrated (biopsychosocial) treatment in the family practice: a pregnant patient with a sacral tumor and severe posttraumatic stress disorder]. / Integrale (biopsychosociale) behandeling in de praktijk: een zwangere patiënte met een sacrumtumor en een ernstige posttraumatische stressstoornis.

In a 25-year-old woman pregnant for the second time after a successful first pregnancy, a locally aggressive, invasive sacrum tumour was diagnosed. The execution of the necessary but potentially mutilating surgical procedures was seriously hampered even during the preparative phase, in spite of the conscious wish of the patient to comply, by her severe psychiatric problems (posttraumatic stress disorder with dissociative symptoms). The Psychiatric Consultation Service took over the case management and an integrated (biopsychosocial) diagnostic investigation was carried out, involving analysis of the problems on four system levels: the biological, the psychological, the social and the health care level. An integrated treatment plan was drafted. By collaboration of the entire multidisciplinary treatment team conditions were secured under which patient would let herself be treated. In this way she was enabled to undergo the necessary procedures, with good results.

[National Health Services in the Netherlands: its influence on dental care]. / Ziekenfonds en tandheelkunde in de 20e eeuw. De tandheelkundige zorgverlening in het perspectief van de Nederlandse wet- en regelgeving.

In the year 1941 the National Health Services Act came into force in which the insured patients have claims to dentistry. The influence on dental care is beyond any doubt and is illustrated by some examples. The dental care for the youth is mentioned in particular. Special attention is paid to legal regulations concerning the application of fluorides.