Lifestyle approaches to hypertension for prevention of stroke and vascular cognitive impairment: a realist review protocol.

INTRODUCTION: Stroke and vascular cognitive impairment (VCI) are major global public health pandemics. The increased incidence of stroke and VCI is in part due to modifiable risk factors (MRFs), with hypertension (HTN) being the strongest single MRF. Even though the underlying causes of HTN are multifactorial, lifestyle choices (eg, poor diet, physical inactivity, alcohol consumption) are chief contributors. Lifestyle medicine (LSM) is a medical and evidence-based discipline that is a promising approach for preventing stroke and cognitive impairment, including VCI. The empirical evidence from systematic reviews, meta-analyses and large population-based studies has reported on the effectiveness of LSM interventions. However, the evaluation of such complex, social and behavioural interventions warrants more information to allow its successful implementation into innovative clinical care models. More importantly, we need to understand how such interventions work, who it works for and under what circumstances to successfully manage HTN and other MRFs (eg, hyperlipidaemia, smoking, alcohol use and diet). METHODS AND ANALYSIS: This realist review will follow the Realist and Meta-narrative Evidence Synthesis: Evolving Standards. The review will comprise four stages: (1) clarify the scope, (2) search for the evidence, (3) critically appraise primary studies and extract data focusing on the context, mechanism and outcome configuration and (4) synthesise evidence and draw conclusions. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this review. The primary output of this review will be an evidence-based programme theory for LSM interventions for the management of HTN and other MRFs to reduce the risk of stroke and VCI. Findings from this review will be disseminated at three levels: micro (eg, patients, caregivers, clinicians, non-research partners), meso (eg, public, national not-for-profit organisations, professional associations and centres) and macro (eg, policymakers and government partners). PROSPERO REGISTRATION NUMBER: CRD42024511566.

Carbapenem and colistin resistance in children with Enterobacteriaceae infections.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging global public health threat. As a reserve agent, colistin has been the drug of choice for the treatment of infections caused by CRE. The aim of this study was to determine the risk factors of carbapenem and colistin-resistant Enterobacteriaceae infections and to investigate the outcomes. METHODS: We conducted a retrospective study in a single university hospital between the years 2013 and 2017 including 150 patients with Enterobacteriaceae infections. RESULTS: Of 150 Enterobacteriaceae infections, 62 (41%) were carbapenem and 23 (15%) were colistin-resistant. Colistin resistance rates among Enterobacteriaceae species increased from 4% in 2014 to 25% in 2017. The inhospital mortality of the patients with colistin-resistant and with carbapenem-resistant infections were 39% (9/23) and 45% (28/62), respectively. Prior exposure to polyantibiotic therapy for Gram negative bacteria was found as a predictor of CRE (OR = 6.4; 95% CI 3.07-13.6; p = 0.001) infections. The median length of hospital stay prior to positive culture (OR = 1.02; 95%CI, 1.0-1.04; p = 0.003) and history of surgery during the admission (OR = 2.46; 95% CI 1.2-5.1; p = 0.005) were found as the predictors of CRE infections. Underlying necrotizing enterocolitis and/or short-bowel syndrome (OR=6.38; 95%CI 1.16-35; p = 0.033) and mechanical ventilation prior to index culture were found as predictors of colistin resistance (OR = 9.4; 95% CI 2-40.4; p = 0.004). CONCLUSIONS: Recognizing the risk factors of carbapenem and colistin resistant Enterobacteriaceae infections is essential in order to conserve carbapenem and colistin since there are no new antibiotics to treat multidrugresistant Enterobacteriaceae infections.

A rare cause of granulomatous hepatitis: Tularemia.

Tularemia is a zoonotic infection caused by Francisella tularensis. Tularemia has several clinical form in humans, including ulceroglandular, pneumonic, oropharyngeal, oculoglandular, and systemic (typhoidal). Tularemia may develop granulomatous and suppurative lesions, especially in the affected regional lymph nodes and various organs. Patients with hepatic involvement typically have elevated transaminase levels, hepatomegaly and rarely jaundice. Histologically, there are typically suppurative microabscesses with occasional surrounding macrophages. Rarely, hepatic granuloma can develop due to tularemia. We present a case of an 8 year-old male residing in a rural village in Turkey, who came to our hospital after having intermittent fever for four months and right upper abdominal pain for two months. Liver had a nodular appearance in liver imaging and liver biopsy were consistent with granulomatous hepatitis. The microagglutination test was positive for tularemia in the patient who was investigated for granulomatous hepatitis etiology. Symptoms and signs improved with tularemia treatment. We present a rare case of hepatic involvement of tularemia in a child. Clinicians should be suspicious of and evaluate for typhoidal tularemia in patients who present with prolonged fever and non-specific systemic symptoms, potentially with associated abdominal pain.

Unicentric Castleman Disease Mimicking an Autoinflammatory Disorder: A Diagnostic Challenge in a Pediatric Patient With Recurrent Fever.

Unicentric Castleman disease (CD) is a rare lymphoproliferative disorder that is characterized by the enlargement of lymph nodes on the neck, mediastinum, and retroperitoneum. Herein, we present a 6-year-old female patient, referred to our medical center because of recurrent fever accompanied by cervical lymphadenopathy and elevated inflammatory markers since 3 years of age. Fever episodes lasting 1 day continued irregularly without any accompanying symptom. MEditerranean FeVer (MEFV) gene analysis showed no mutations; however, as inflammatory markers including serum amyloid A remained markedly high during attack-free periods, colchicines was initiated. The patient did not respond to maximally tolerated doses of colchicine; therefore, we added canakinumab and systemic methylprednisolone, subsequently. Unresponsiveness to 3 doses of bimonthly canakinumab and new-onset hepatosplenomegaly led us to investigate large-vessel vasculitis and malignancy; therefore, we performed Position emission tomography, which further revealed a hypermetabolic retroperitoneal solid mass. After performing the excisional biopsy, the patient has been diagnosed as suffering from hyaline vascular variant CD, confirmed by histopathology. In conclusion, we report a pediatric unicentric CD, which resembled autoinflammatory diseases and responded well to surgical resection, with the normalization of inflammatory markers 1 month after the procedure. CD, even the unicentric and hyaline vascular variant, should be considered in the differential diagnosis of the patients with an autoinflammatory phenotype.

Clinical findings and genetic analysis of the patients with IL-12Rß1 deficiency from southeast Turkey.

Dogruel D, Gündeslioglu ÖÖ, Yilmaz M, Alabaz D, Altintas DU, Kocabas E. Clinical findings and genetic analysis of the patients with IL- 12Rß1 deficiency from southeast Turkey. Turk J Pediatr 2019; 61: 174-179. IL-12Rß1 deficiency is an autosomal recessive disorder characterized by predisposition to poorly pathogenic mycobacteria, salmonella and candida species. We aimed to analyze the clinical manifestations, immunological and genetic features of IL-12Rß1 deficiency in 10 Turkish patients from a single center. We retrospectively studied the clinical manifestations and genetic analysis of the IL-12Rß1 deficiency patients from 2008 to 2016. Ten patients were diagnosed and followed for eight years. The mean age at onset and diagnosis were 24.1±42.5 (med:10.5) and 52.3±6.83 (med:20) months, respectively. Parental consanguinity rate was 81.8%. All patients were BCG vaccinated. Abscess and axillary lymphadenopathy in the vaccinated area was the most common initial presentation following the BCG vaccination, six patients had recurring oral candidiasis. Active infections were treated appropriately, in addition to prophylactic therapy with IFNÉ£. We identified 6 different mutations in the IL12RB1 gene in 10 patients including 5 splice-site mutations, 3 missense, 1 frameshift, 1 premature stop codon. One of these mutations was novel. The most common mutation was IVS8+1G > A(c.783+1G > A) followed by p.R175W(c.523C > T). This study emphasizes that patients presented with abscess and axillary lymphadenopathy associated with BCG vaccination should be evaluated for IL-12Rß1 deficiency.

Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey.

OBJECTIVES: The aim of this point prevalence survey was to evaluate the consumption, indications and strategies of antifungal therapy in the paediatric population in Turkey. METHODS: A point prevalence study was performed at 25 hospitals. In addition to general data on paediatric units of the institutes, the generic name and indication of antifungal drugs, the presence of fungal isolation and susceptibility patterns, and the presence of galactomannan test and high-resolution computed tomography (HRCT) results were reviewed. RESULTS: A total of 3338 hospitalised patients were evaluated. The number of antifungal drugs prescribed was 314 in 301 patients (9.0%). Antifungal drugs were mostly prescribed in paediatric haematology and oncology (PHO) units (35.2%), followed by neonatal ICUs (NICUs) (19.6%), paediatric services (18.3%), paediatric ICUs (PICUs) (14.6%) and haematopoietic stem cell transplantation (HSCT) units (7.3%). Antifungals were used for prophylaxis in 147 patients (48.8%) and for treatment in 154 patients (50.0%). The antifungal treatment strategy in 154 patients was empirical in 77 (50.0%), diagnostic-driven in 29 (18.8%) and targeted in 48 (31.2%). At the point of decision-making for diagnostic-driven antifungal therapy in 29 patients, HRCT had not been performed in 1 patient (3.4%) and galactomannan test results were not available in 12 patients (41.4%). Thirteen patients (8.4%) were receiving eight different antifungal combination therapies. CONCLUSION: The majority of antifungal drugs for treatment and prophylaxis were prescribed in PHO and HSCT units (42.5%), followed by ICUs. Thus, antifungal stewardship programmes should mainly focus on these patients within the availability of diagnostic tests of each hospital.

Clinical and epidemiological features of Turkish children with 2009 pandemic influenza A (H1N1) infection: experience from multiple tertiary paediatric centres in Turkey.

BACKGROUND: In April 2009 a novel strain of human influenza A, identified as H1N1 virus, rapidly spread worldwide, and in early June 2009 the World Health Organization raised the pandemic alert level to phase 6. Herein we present the largest series of children who were hospitalized due to pandemic H1N1 infection in Turkey. METHODS: We conducted a retrospective multicentre analysis of case records involving children hospitalized with influenza-like illness, in whom 2009 H1N1 influenza was diagnosed by reverse-transcriptase polymerase chain reaction assay, at 17 different tertiary hospitals. RESULTS: A total of 821 children with 2009 pandemic H1N1 were hospitalized. The majority of admitted children (56.9%) were younger than 5 y of age. Three hundred and seventy-six children (45.8%) had 1 or more pre-existing conditions. Respiratory complications including wheezing, pneumonia, pneumothorax, pneumomediastinum, and hypoxemia were seen in 272 (33.2%) children. Ninety of the patients (11.0%) were admitted or transferred to the paediatric intensive care units (PICU) and 52 (6.3%) received mechanical ventilation. Thirty-five children (4.3%) died. The mortality rate did not differ between age groups. Of the patients who died, 25.7% were healthy before the H1N1 virus infection. However, the death rate was significantly higher in patients with malignancy, chronic neurological disease, immunosuppressive therapy, at least 1 pre-existing condition, and respiratory complications. The most common causes of mortality were pneumonia and sepsis. CONCLUSIONS: In Turkey, 2009 H1N1 infection caused high mortality and PICU admission due to severe respiratory illness and complications, especially in children with an underlying condition.

[New approaches in antibiotic therapies in chronic pulmonary diseases]. / Cocuklarda kronik akciger hastaliklarinin antibiyotik tedavisinde yeni yaklasimlar.

Chronic lung diseases are one of the considerable problems in childhood both for physicians and patients. Due to early diagnosis of illness and complications; advances at vaccination methods and antibiotic therapies; life period of patients have been prolonged so not only at childhood but at adults, chronic lung diseases seem to be important healthy problem. One of the most important factors affecting to prognosis of the diseases are concominant infections. This review is an argument of antibiotic usage regimens at cystic fibrosis, bronchiectasis and allergic bronchopulmonary aspergillosis which are the most usual chronic lung diseases seen at childhood and adults.

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis.

Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3rd and 7th days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT > or = 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha > or = 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. It was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease.

The value of a new microculture method for diagnosis of visceral leishmaniasis by using bone marrow and peripheral blood.

We have demonstrated that the microculture method (MCM) enables the diagnosis of visceral leishmaniasis (VL) with samples from both the bone marrow (BM) and peripheral blood (PB). The MCM is superior to the traditional culture method (TCM) as determined by its higher sensitivity in the detection of promastigotes and the more rapid time for emergence of promastigotes. The sensitivity of MCM (100% in BMs and 77.8-100% in PB) was considerably higher than that of the TCM (37.5-100% in BMs and 0-100% in PB) according to decreasing parasite density (P < 0.05). The concentration of parasites in buffy coats has increased the sensitivity of both methods, especially that of the MCM. Detection of promastigotes by MCM requires lower amounts of culture media (25-50 microL) and shorter incubation periods (2-7 days) than TCM (2.5-3.5 mL and 15-35 days, respectively). MCM was found to be valuable with the advantages of simplicity and sensitivity, in addition to being cost-effective in the routine diagnosis for VL in Adana Turkey.