V državah z dobro vzpostavljenimi cepilnimi programi je cepljenje “žrtev lastnega uspeha”, saj je nizka pojavnost bolezni, ki jih preprečujemo s cepljenjem, zmanjšala izkušnjo njihovega bremena in s ...tem očitnost koristi cepljenja. Povečevanje števila staršev, ki zavračajo cepljenje svojih otrok, je že ogrozilo t. i. skupnostno imunost oz. jo zmanjšalo celo do mere, da so se ponovno začeli pojavljati izbruhi prej obvladanih nalezljivih bolezni. V prispevku predstavljamo sistematični pristop k etičnim vprašanjem glede cepljenja otrok skozi štiri principe biomedicinske etike (tj. spoštovanje posameznikove avtonomije, neškodovanje, dobrodelnost in pravičnost), ki je razumljiv model za razmislek o tovrstnih vprašanjih. Pediatrom na primarni ravni, ki se najpogosteje srečujejo z dilemami glede obravnave otrok, katerih starši zavračajo cepljenje, je lahko sistematičnost opisanega pristopa v pomoč pri etičnem razmisleku, odločanju in iskanju lastne vloge v tovrstnih situacijah. Utemeljujemo iskanje “etičnega ravnovesja”, kar pomeni, da stopnja spoštovanja avtonomije staršev ni stalna, ampak odvisna od ravni vzpostavljene skupnostne imunosti. če moralna dolžnost posameznikov, da prispevajo k imunosti populacije, ni izpolnjena, je upravičeno s strani države pred-pisano obvezno cepljenje. Država je namreč odgovorna za varovanje skupnostne imunosti, ki jo moramo razumeti kot javno dobro in zato potrebuje posebno državno zaščito.
Presejalno testiranje novorojenčkov (PTN) je ena svetovnih javnozdravstvenih zgodb o uspehu. Izvaja se v veliki večini razvitih držav sveta, razlikuje pa se le po obsegu in usmeritvah testiranja. ...Najbolj obsežni programi presejalnega testiranja na svetu obsegajo testiranje na več kot 50 različnih bolezni. PTN v Sloveniji je ključni del javnozdravstvenega sistema s pričetkom v letu 1979 s testiranjem na fenilketonurijo. V letu 1981 se je dodalo testiranje na kongenitalno hipotirozo. Program se je razvijal in širil z uvedbo novih tehnologij, kot so masna spektrometrija za bolezni presnove in imunoreaktivni ter genetski testi za bolezni, kot so cistična fibroza, kongenitalna adrenalna hiperplazija, spinalna mišična atrofija in primarne imunske pomanjkljivosti. Odvzem vzorca, posušen madež krvi na filter papirju, omogoča enostaven transport v laboratorij Pediatrične klinike v Ljubljani, kjer poteka analiza. Strokovno izvedeni odvzem, ki ga opravi osebje porodnišnic, zagotavlja ustrezno kakovost vzorcev in je pogoj za uspešno izvedbo testiranja. Vključenost v program je univerzalna za vse novorojenčke, z možnostjo zavrnitve s strani staršev. Do danes smo v Sloveniji uspešno odkrili in zdravili več 100 novorojenčkov, kar potrjuje njegov pomen. Z odkritjem novih zdravil in terapij bo obseg PTN naraščal. Uspešnost programa pa je neposredno odvisna od sinergije sodelujočih skupin – porodnišnic, pediatrične klinike in laboratorija.
Abstract Background Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those who are unaffected. ...Data for identification of FH with a universal screening for hypercholesterolemia in children are lacking. Objectives This study sought genetic identification of FH from a cohort of children with elevated serum total cholesterol (TC) concentration, detected in a national universal screening for hypercholesterolemia. Methods Slovenian children born between 1989 and 2009 (n = 272) with TC >6 mmol/l (231.7 mg/dl) or >5 mmol/l (193.1 mg/dl) plus a family history positive for premature cardiovascular complications, identified in a national universal screening for hypercholesterolemia at 5 years of age were genotyped for variants in LDLR , PCSK9 , APOB , and APOE. Results Of the referred children, 57.0% carried disease-causing variants for FH: 38.6% in LDLR , 18.4% in APOB , and none in PCSK9 . Nine novel disease-causing variants were identified, 8 in LDLR , and 1 in APOB . Of the remaining participants, 43.6% carried the APOE E4 isoform. Estimated detection rate of FH in the universal screening program from 2009 to 2013 was 53.6% (95% confidence interval CI: 34.5% to 72.8%), peaking in 2013 with an upper estimated detection rate of 96.3%. Variants in LDLR , APOB , or the APOE E4 isoform occurred in 48.6%, 60.0%, and 76.5%, respectively, of patients with a family history negative for cardiovascular complications. Conclusions Most participants who were referred from a national database of universal screening results for hypercholesterolemia had genetically confirmed FH. Data for family history may not suffice for reliable identification of patients through selective and cascade screening.
In the last two decades, the introduction of tandem mass spectrometry in clinical laboratories has enabled simultaneous testing of numerous acylcarnitines and amino acids from dried blood spots for ...detecting many aminoacidopathies, organic acidurias and fatty acid oxidation disorders. The expanded newborn screening was introduced in Slovenia in September 2018. Seventeen metabolic diseases have been added to the pre-existing screening panel for congenital hypothyroidism and phenylketonuria, and the newborn screening program was substantially reorganized and upgraded.
Tandem mass spectrometry was used for the screening of dried blood spot samples. Next-generation sequencing was introduced for confirmatory testing. Existing heterogeneous hospital information systems were connected to the same laboratory information system to allow barcode identification of samples, creating reports, and providing information necessary for interpreting the results.
In t he first y ear of t he expanded newborn screening a total of 15,064 samples w ere screened. Four patients were confirmed positive with additional testing.
An expanded newborn screening program was successfully implemented with the first patients diagnosed before severe clinical consequences.
Mukopolisaharidoze so lizosomske bolezni kopičenja, pri katerih se klinična slika razvija postopno. Bolezni napredujejo in prizadenejo številne organe. S trenutno dostopnimi možnostmi zdravljenja ...bolnikov ne moremo ozdraviti, a s prihodom genskega zdravljenja ob pravočasni postavitvi diagnoze in zgodnjem zdravljenju lahko upamo tudi na to možnost. V prispevku predstavljamo primera bolnikov s polisaharidozo. V prvem primeru opisujemo dečka, pri katerem je prisotnost bolezni pri starejšem bratu odprla možnost pra-vočasne postavitve diagnoze in vključitev v eksperimentalno gensko zdravljenje v tujini, ki se po do sedaj opravljenih preiskavah kaže kot učinkovita. V drugem primeru gre za dečka, pri katerem so po kliničnem sumu in ustreznem diagnosticiranju bolezen potrdili relativno zgodaj in s tem omogočili eksperimentalno gensko zdravljenje v tujini. V opisanih primerih gre torej za dva izmed prvih petih primerov uspešno izpeljanega genskega zdravljenja pri slovenskih bolnikih, ki za zdaj še poteka v okviru raziskovalnega protokola v tujini. Gensko zdravljenje torej postopno, a nezadržno postaja del klinične realnosti. Pogoj za uspešno zdravljenje mukopolisaharidoze z genskim zdravljenjem je, da bolezen čim prej prepoznamo, kar bo v prihodnosti verjetno uresničljivo z uvedbo programa presejanja novorojenčkov.
Mukopolisaharidoze so skupina lizosomskih bolezni kopičenja. Njihova skupna značilnost je pomanjkanje delovanja encimov, ki razgrajujejo glikozaminoglikane, polisaharide, ki se povezujejo s ...proteoglikani in tvorijo zunajcelični matriks. Ker ni encimov, ki bi glikozaminoglikane razgrajevali, se ti kopičijo v lizosomih in povzročijo njihovo okvaro in zato se okvarijo drugi celični organeli, celice in končno organi. Klinična slika je široka, od nevro-kognitivnega upada, skeletno-mišičnih deformacij in tipičnih obraznih sprememb. Ključno je zgodnje prepoznavanje bolezni, čeprav s trenutno dostopnimi načini zdravljenja bolezni ne moremo ozdraviti, lahko pa le upočasnimo njen potek, kar je najbolj učinkovito v fazi bolezni še pred pojavom simptomov. Obetavni način zdravljenja je gensko zdravljenje, ki nakazuje možnost ozdravitve bolezni.Predstavljamo primer dečka, pri katerem je bil prepoznan zgodnji kognitivni upad in za bolezen tipične spremembe. Napoten je bil v terciarno ustanovo, kjer je bila diagnoza potrjena. Deček je bil julija 2018 zdravljen z eksperimentalnim genskim zdravljenjem v tujini (bolnišnica San Raffaele, Milano, Italija). V opisanem primeru gre po našem vedenju za prvo uspešno izpeljano gensko zdravljenje pri slovenskih bolnikih ter za enega prvih primerov genskega zdravljenja mukopolisaharidoze tipa I v svetovnem merilu. Gensko zdravljenje s tem postaja del nove klinične stvarnosti, kar predstavlja pomemben mejnik za naš prostor. Zaradi naprednih zdravljenj bi bilo v prihodnosti smiselno uvesti presejalno testiranje novorojenčkov za MPS tipa I, ki se pri nas ali v Evropi doslej še ne izvaja. Do tedaj pa ostaja najpomembnejši predpogoj za uspešno zdravljenje zgodnja klinična prepoznava bolezni in napotitev v terciarno zdravstveno ustanovo.
Background Healthcare professionals (HCPs), patients and families are often faced with ethical dilemmas. The role of healthcare ethics committees (HECs) is to offer support in these situations. Aim ...The primary objective was to study how often HCPs encounter ethical dilemmas. The secondary objective was to identify the main types of ethical dilemmas encountered and how HCPs solve them. Subjects and methods We conducted a cross-sectional, survey-based study among HCPs in 14 Slovenian hospitals. A questionnaire was designed and validated by HCPs who were selected by proportional stratified sampling. Data collection took place between April 2015 and April 2016. Results The final sample size was n = 485 (385 or 79.4%, female). The response rates for HCPs working in secondary and tertiary level institutions were 45% and 51%, respectively. Three hundred and forty (70.4%) of 485 HCPs (very) frequently encountered ethical dilemmas. Frequent ethical dilemmas were waiting periods for diagnostics or treatment, suboptimal working conditions due to poor interpersonal relations on the ward, preserving patients' dignity, and relations between HCPs and patients. Physicians and nurses working in secondary level institutions, compared to their colleagues working in tertiary level institutions, more frequently encountered ethical dilemmas with respect to preserving patients' dignity, protecting patients' information, and relations between HCPs and patients. In terms of solutions, all HCPs most frequently discussed ethical dilemmas with co-workers (colleagues), and with the head of the department. According to HCPs, the most important role of HECs is staff education, followed by improving communication, and reviewing difficult ethical cases. Conclusions Waiting periods for diagnostics and treatment and suboptimal working conditions due to poor interpersonal relations are considered to be among the most important ethical issues by HCPs in Slovenian hospitals. The most important role of HECs is staff education, improving communication, and reviewing difficult ethical cases.
Familial hypercholesterolemia (FH) is arguably the most common monogenic disorder in humans, but severely under-diagnosed. Individuals with untreated FH have an over 10-fold elevated risk of ...cardiovascular complications as compared to unaffected individuals; early diagnosis and timely management substantially reduce this risk.
Slovenia has gradually implemented the program of universal FH screening in pre-school children, consisting of a two step approach: (1) universal hypercholesterolemia screening in pre-school children at the primary care level; (2) genetic FH screening in children referred to the tertiary care level according to clinical guidelines (with additional cascade screening of family members). The program is presented in detail.
We analyzed retrospective data (2012–2016), to assess the efficiency of the universal FH screening program. In that period, 280 children (59.3% female) were referred to our center through the program for having TC > 6 mmol/L (231.7 mg/dL) or >5 mmol/L (193.1 mg/dL), with a positive family history of premature cardiovascular complications at the universal hypercholesterolemia screening.
170 (57.1% female) of them were fully genotyped, 44.7% had an FH disease-causing variant (28.8% in LDLR gene, 15.9% in APOB, none in PCSK9), one patient was LIPA positive, and 40.9% of the remaining patients carried an ApoE4 isoform; genetic analysis is still ongoing for one-third of the referred patients. For almost every child with confirmed FH, one parent had highly probable FH.
FH was confirmed in almost half of the referred children, detected through the universal screening for hypercholesterolemia.
•FH is a common monogenic disorder but severely under diagnosed and under treated.•FH screening in childhood with early treatment is needed.•Slovenia has a unique and effective program of universal FH screening in children.•Almost half of the children referred through the program had FH causing mutation.
Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. ...Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in one of the causative genes (
,
,
). In polygenic hypercholesterolemia (PH), the disease-causing genetic variant is absent; it is likely the cumulative result of multiple single nucleotide polymorphisms in LDL metabolism-related genes and other factors, such as lifestyle and environment. In high risk groups, such as patients with FH, an effective primary prevention of CVD must begin in childhood. High-sensitivity C-reactive protein (hsCRP) and carotid intima media thickness (cIMT) are two potential minimally invasive correlates of inflammation and subclinical atherosclerosis progression. hsCRP and cIMT have been shown to be significantly increased in patients with FH and PH relative to healthy controls, with some studies yielding conflicting results. In this review, we aim to summarize current knowledge and recent findings regarding the applicability of hsCRP and cIMT as markers of low-grade inflammation and subclinical atherosclerosis, focusing especially on children and adolescents with hypercholesterolemia.
Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D ...are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.
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