Parental psychological distress associated with COVID-19 outbreak: A large-scale multicenter survey from Turkey

Aims: Pandemics can cause substantial psychological distress; however, we do not know the impact of the COVID-19 related lockdown and mental health burden on the parents of school age children. We aimed to comparatively examine the COVID-19 related the stress and psychological burden of the parents with different occupational, locational, and mental health status related backgrounds. Methods: A large-scale multicenter online survey was completed by the parents (n = 3,278) of children aged 6 to 18 years, parents with different occupational (health care workers—HCW [18.2%] vs. others), geographical (İstanbul [38.2%] vs. others), and psychiatric (child with a mental disorder [37.8%]) backgrounds. Results: Multivariable logistic regression analysis showed that being a HCW parent (odds ratio 1.79, p <.001), a mother (odds ratio 1.67, p <.001), and a younger parent (odds ratio 0.98, p =.012); living with an adult with a chronic physical illness (odds ratio 1.38, p <.001), having an acquaintance diagnosed with COVID-19 (odds ratio 1.22, p =.043), positive psychiatric history (odds ratio 1.29, p <.001), and living with a child with moderate or high emotional distress (odds ratio 1.29, p <.001; vs. odds ratio 2.61, p <.001) were independently associated with significant parental distress. Conclusions: Parents report significant psychological distress associated with COVID-19 pandemic and further research is needed to investigate its wider impact including on the whole family unit. © The Author(s) 2020

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

INVESTIGATION ON THE EFFICACY OF FECAL MICROBIOTA TRANPLANTATION IN CATS WITH ATAXIA

FELİN ATAKSİ SENDROMUNDA FEKAL MİKROBİYOTA TRANSPLANTASYONUNUN ETKİNLİĞİNİN ARAŞTIRILMASI Adak H.İ Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü İç Hastalıkları Programı Yüksek Lisans Tezi, Aydın, 2019. Yapılmış olan çalışmalarda ve litaratür taramalarında nörolojik defisiti bulunan canlılarda bağırsak mikrobiyotasında disbiyozis olduğu tesbit edilmiştir. Bu çalışmada ataksik kedilerde bağırsak mikrobiyotasını Fekal Mikrobiyota Transplantasyonuyla (FMT) restore ederek var olan hastalığın semptomlarının geriletilmesi ve/veya hastalığın iyileştirilmesi amaçlanmıştır. Genel muayenesi yapılan ve klinik bakıda her hangi bir sağlık problemi belirlenmeyen (hasta hayvanlar ile aynı yaş gruplarından) donörden dışkı örnekleri alındı. Alınan dışkı örnekler sedimentasyon/flotasyon yöntemiyle parazitolojik olarak incelenmiş ve her hangi bir sestod, nematod ve protozoona rastlanmayanlar dışkı örnekleri kullanılmıştır. Ortalama olarak her hasta için donörlerden 20 gr dışkı örneği alınmış olup öncelikle dışkı % 0,9 NaCl (ortalama 50-100 ml) ile sulandırılıp homojenize hale getirildi. Sonrasında büyük partiküllerin ayrılması amacıyla bir süzgeç yardımıyla hazırlanan solüsyon büyük partiküllerden ayırılmıştır. İlk yarım saat içerisinde dışkı hasta hayvanlara rektal yolla (serum seti aracılığında) transplante edildi. Üç gün ara ile toplamda 5 uygulama yapılıp hasta hayvanlarda genel durum gözlemlendi.Çalışmaya dahil edilen 10 kedide klinik bulgu olarak paraliz, tremor, inkordinasyon, eliptik yürüyüş gözlemlendi. Transpantasyon uygulamaları sonrasında 10 vakanın tamamında klinik bulgularda iyileşme veya gerileme gözlemlendi ve nörolojik muayene eşliğinde transpantasyon öncesi ve sonrası hastanın Modifiye Glasgow Koma Skoru verileri karşılaştırıldı. Yapılan istatistiksel değerlendirme sonucunda (sağaltım öncesi ile sonrası median ± standart sapma) bakımından motor aktivite [5 ± 1.07 ile 6 ± 0.32] , bilinç seviyesi [4.5 ± 1.35 ile 6 ± 0], beyin sapı refleksi [5 ± 0.74 ile 6 ± 0] olarak tespit edilmiştir. İstatistiksel değerlendirme sonucu (sağaltım öncesi ile sonrası ortalama değer ± standart sapma) bakımından motor aktivite [4.4 ± 1.07 ile 5.9 ± 0.3], bilinç seviyesi [4.5 ± 1.35 ile 6 ± 0], beyin sapı refleksi [4.9 ± 0.7 ile 6 ± 0] olarak belirlenmiştir. Sonuç olarak ataksisi mevcut kedilerde FMT ile sızıntılı bağırsağa ait muhtemel intestinal permeabilite artışı ile nöroinflamasyonun önlenebileceği, mikrobiyotanın restore edilmesi ile bağırsakta mikrobiayatada biyoçeşitliliğin azalmasına ilişkin nörotransmiter bağlantılı metabolitlerin seviyelerindeki değişimlerinde önüne geçilerek bağırsak-beyin ekseninde olumsuz iletişimin ya da beyin fonksyionarı üzerindeki olumsuz etkileşimin engellenebileceği öne sürülebilir. Bu çalışma Adnan Menderes Üniversitesi Bilimsel Araştırma Projeleri tarafından VTF-19001 nolu proje ile desteklenmiştir.INVESTIGATION ON THE EFFICACY OF FECAL MICROBIOTA TRANPLANTATION IN CATS WITH ATAXIA Adak H.İ Adnan Menderes University Institute of Health Sciences Internal Medicine Program, Aydın, 2019 In the researches and literature survey, it was found that there was dysbiosis within te microbiata within organisms presenting neurological deficits. Accompanied with this information it was aimed to restore the intestinal microbiata of ataxic cats with Fecal Microbial Transplantation (FMT) in an attempt to alleviate the symptoms of the existing disease and/or to improve the disease. Stool samples were taken from the donor (from the same age groups as the sick animals) without any health problems as detected by general examination and clinical approach. Obtained fecal samples were parasitologically examined via sedimentation/flotation method and to those of samples were used without any cestode, nematode and protozoa. On average, 20 gr stool samples were taken from each donor for each patient which was initally diluted with 0.9% NaCl (50-100 ml) and homogenized. The solution was then separated from large particles using a strainer to remove large particles. In the first half-hour, the stool was transplanted via rectal route (by serum set) into sick animals. A total of 5 treatments were performed within 3 days intervals and general conditions were observed in the animals. Paralysis, tremor, incoordination, elliptic gait were observed as clinical findings in 10 cats with ataxia included in the study. All 10 cases showed improvement or regression of clinical findings after transplanation, and the modified Glasgow Coma Score data of the patient were compared before and after transplanation with neurological examination. As a result of the statistical evaluation (median ± standard deviation before and after treatment) motor activity [5 ± 1.07 to 6 ± 0.32], level of consciousness [4.5 ± 1.35 to 6 ± 0], brain stem reflex [5 ± 0.74 to 6 ± 0 ] determined. Statistical evaluation (mean value ± standard deviation before and after treatment) motor activity [4.4 ± 1.07 to 5.9 ± 0.3], level of consciousness [4.5 ± 1.35 to 6 ± 0], brain stem reflex [4.9 ± 0.7 ± 6 ± 0] determined. In conclusion to those of cats with ataxia, FMT should have prevent intestinal permability increase and neuroinflammation probably due to leaky gut; within the restoration of microbiata, prevention of alterations among metabolite levels in relationship with neurotransmitter due to microbiata diversity thus intercept the negative crosstalk between gut-brain axis or interaction beyond brain functions. This study was supprted by Adnan Menderes University Research Funding Unit with Project no: VTF-19001.İÇİNDEKİLER TEŞEKKÜR i İÇİNDEKİLER iii SİMGELER VE KISALTMALAR DİZİNİ viii ŞEKİLLER DİZİNİ ix TABLOLAR DİZİNİ xiii ÖZET xv ABSTRACT xvii 1.GİRİŞ 1 2. GENEL BİLGİLER 3 2.1.Ataksinin tanımı 3 2.2. Ataksi Çeşitleri 3 2.2.1. Serebellar ataksi 4 1.2.2. Vestibuler ataksi 4 1.2.3.Duyusal (spinal veya genel proprioseptif) ataksi 5 1.3.Kedilerde Generalize Ataksilerin Sebepleri 11 1.3.1.Feline Enfeksiyöz Peritonitis: 11 1.3.2.Metronidazol Toksisitesi: 12 1.3.3.Lizozomal Depolama Hastalıkları: 13 1.3.4.Serebellar hipoplazi: 14 1.3.5. İntrakranial İntra-Araknoid Kistler 15 1.3.6.Otitis media/interna 16 1.3.7.İdiopatik vestibuler sendrom 17 1.3.8. Aminoglikozid antiboyotikler 18 1.3.9. Konjenital vestibular sendrom 18 1.4. Küçük Hayvanlarda Nörolojik Muayene 19 1.4.1. Hastanın geçmişi 20 1.4.2. Fiziksel Muayene 21 1.4.3. Nörolojik muayene 21 1.4.4. Gözlem 21 1.4.5. Bilinç, farkındalık, davranış 22 1.4.6. Duruş ve vücut pozisyonu 23 1.4.7. Yürüyüşün Değerlendirilmesi 25 1.4.8.Elle Muayene 27 1.4.8.1.Kranyal sinir muayenesi 27 1.4.8.1.2.Olfaktör Sinir - (CN I) 27 1.4.8.1.3. Okülomotor Sinir (CN III) 29 1.4.8.1.4. Troklear sinir (CN IV) 30 1.4.8.1.5. Trigeminal sinir (CN V) 30 1.4.8.1.6. Abdusent sinir (CN VI) 31 1.4.8.1.7. Fasial sinir (CN VII) 31 1.4.8.1.8. Vestibulocochlear sinir (CN VIII) 32 1.4.8.1.9.Glossopharyngeal sinir (CN IX) ve Vagus siniri (CN X) 32 1.4.9. Postüral reaksiyonlar 36 1.4.9.1. Proprioseptif yerleştirme 36 1.4.9.2. Propioseptif Atlama 38 1.4.9.3. Yerleştirme yanıtı 39 1.4.9.4. Omurga refleksleri 40 1.4.9.5. Pelvik kollarda çekilme refleksi 41 1.4.9.6. Patellar refleks 42 1.4.9.7. Torasik kollarda geri çekilme refleksi 43 1.4.9.8. Perineal refleks 43 1.4.9.9. İdrar kesesi palpasyonu 44 1.4.9.10. Duyusal değerlendirme 44 1.4.9.11.Nosisepsiyon testi 44 1.4.9.12. Kutanöz trunci refleksi (pannikulus) 45 1.5. Sağaltım 45 1.5.1. Antikonvülzan 45 1.5.1.1. Fenobarbital 45 1.5.1.2.Bromit 46 1.5.1.3.Zonisamit 47 1.5.1.4. Levetirasetam 48 1.5.1.5. Felbamat 48 1.5.1.6. Gabapentin 49 1.5.1.7.Klorazepat 49 1.5.1.8.Diazepam 50 1.5.1.9.Topiramat 51 1.5.2.Alternatif Sağaltım Yöntemi 51 1.5.2.1.Fekal Transplantasyon 51 1.5.2.1.1-) Küçük Hayvanlarda Fekal Mikrobiyota Nakli Uygulamaları 52 1.5.2.1.2-)Mekanizma 52 1.5.2.1.3-)Endikasyonları 53 1.5.2.1.4-)Donör seçimi 54 1.5.2.1.5-)Hazırlık 54 1.5.2.1.6-)Yönetim 55 1.5.2.2.Mikrobiyota-Bağırsak-Beyin Aksı 56 1.5.2.1.3. Mikrobiyota ve Nörodejenerasyon 58 3. GEREÇ VE YÖNTEM 61 3.1. Hayvan Materyali 61 3.2.Dışkı Örneklerinin Toplanması ve Hazırlanması 61 3.3. Klinik ve Nörolojik Muayene 67 3.3.1.Gözlem Genel Bilgi 67 3.3.1.1.Gözlem Klinik Muayene 68 3.3.2.Kranial sinirler genel bilgiler 69 3.3.2.1.Tehdit Tepkisi 71 3.3.2.2.Pupil Işık Refleks 72 3.3.2.3.Strabizmin Değerlendirilmesi 73 3.3.2.4.Palpebral Refleks 74 3.3.2.5. Okülosefalik Refleks / Fizyolojik Nistagmus 75 3.3.3. Postural reaksiyonlar genel bilgiler 76 3.3.3.1.Postural reaksiyonlar klinik muayene 77 3.3.4.Omurga refleksleri genel bilgiler 80 3.3.4.1.Anal Sfinkter Refleks 81 3.3.4.2.Pedal fleksör rekleks 81 3.3.4.3.Patella Refleks 82 3.3.4.4.Kutanöz hissi ve ağrı genel bilgi 83 3.3.4.4.1. .Kutanöz hissi ve ağrı klinik muayene 84 3.4.Modifiye Glasgow koma skorlaması 85 3.4.1.Modifiye Glasgow koma skoru nedir? 85 3.4.1.1.Bilinç seviyesi 86 3.4.1.2.Duruş ve uzuv motor fonksiyonu 87 3.4.1.3.Beyin sapı refleksleri 87 3.4.2.Koma Ölçeğinin Uygulanması 88 3.5. İstatistiksel değerlendirme 89 4.BULGULAR 90 5.TARTIŞMA 159 6.SONUÇ VE ÖNERİLER 166 KAYNAKLAR 167 ÖZGEÇMİŞ 18