Auricula (during 2012.01.01–2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19–7.06) per 100 treatment years in all patients and 11.27 (CI 9.96–12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age , earlier major bleeding , COPD  and previous stroke  or transient ischemic attack (TIA) . Prior warfarin treatment was protective . This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register The online version of this article (10.1007/s11239-020-02319-w) contains supplementary material, which is available to authorized users. Register study to examine risk factors for major bleeding on NOAC-treatment due to VTE.High age, history of major bleeding, COPD and previous stroke or TIA increase the risk of major bleeding.Previous anticoagulation with warfarin confers lower bleeding risk.The rate of major bleeding is especially high among elderly (11.27 per 100 treatment years).The incidence of first VTE in the general population is about 0.1% per year . Total mAuricula has over 150 000 active patients, the coverage ratio is estimated to be about 50% with no apparent selection bias, NOAC represents about half of the treatment years and the VTE indication constitutes 18% of all patients with oral anticoagulation [NPR contains diagnoses defined as ICD-10 codes on hospital admissions and outpatient clinics for patients with a Swedish personal identity number. About 99% has a valid personal number and current absence of primary diagnosis at hospital admission or in outpatient clinics is only 0.9% and 3.2% respectively [CDR consists of all identified deaths in Sweden with a personal identity number and information includes age, sex, date and cause of death.The study was approved by the ethical research committee in Umeå, Dnr 2015/145-31. Data were collected from the Swedish national quality register for oral anticoagulation (Auricula), the Swedish National Patient Register (NPR) and The Cause of Death Register (CDR). According to the latest published yearly report Auricula was used to find patients on treatment with NOAC due to a physician reported VTE between 2012.01.01 and 2017.12.31. Individual patients could only be included once, therefore, in patients registered several times, only the first treatment period was included. Using personal identity number included patients where then identified in the NPR and the CDR to find characteristics at baseline and endpoints (see Appendix A for ICD-10 definitions). Both primary and secondary diagnosis were used to maximize baseline characteristics and to avoid missing possible endpoints. Characteristics at baseline data were collected and compared for bleeders and non-bleeders as well as for different age groups  using non-parametric tests . Primary endpoint was major bleeding defined as bleeding leading to inpatient or specialized outpatient hospital care. Patients contributed with follow-up time for major bleeding until that endpoint occurred or until the end of 2017. Follow-up also ended in the event of death or if treatment stopped or changed in terms of dosage or substance. Major bleedings were subcategorized if ICD-coded as gastrointestinal or intracranial. Any bleeding that led to hospital care was termed as other bleeding. R Core Team  was used for data analysis. Incidence rates were calculated for bleeding end-points  in all patients and for the different age groups. Cumulative risk of bleeding end-points were presented with Kaplan Meier survival curves. Both univariate and multivariate Cox regression tests were used to screen possible risk or protective factors for major bleeding. 95% confidence intervals were used.In this study In total 18 219 patients with NOAC-treated deep vein thrombosis (DVT) or pulmonary embolism (PE) were included in the study. The mean age was 69.3 years and 52.4% were males. Among included patients 38.8% had acute DVT, 9.1% had recurrent DVT, 40.5% had acute PE, 5.3% recurrent PE and 6.3% DVT or PE not classified as acute or recurrent. The majority had a VTE for the first time (85.6%). The overall distribution of NOAC substances were rivaroxaban 54.8%, apixaban 42.0%, dabigatran 3.2% and edoxaban 0.1%. Low dose NOAC  was used in 13.2% of the patients. The median follow-up time was 183 days (IQR 92-360). Characteristics at baseline when NOAC-treatment was started are presented for all patients in Table Among the 18,219 patients 938 had a major bleeding and the rate of major bleeding was 6.62 (95% CI 6.19–7.06) per 100 treatment years. Intracranial bleeding was found in 81 patients, 293 patients had gastrointestinal and 590 patients other bleedings, with corresponding bleeding rates of 0.55 (CI 0.43–0.67), 2.00 (CI 1.77–2.24) and 4.11 (CI 3.77–4.45) respectively. Major bleeding rate for patients under 60 years was 3.40 (CI 2.84–3.97), between 60 and 80 years 6.85 (CI 6.23–7.47) and over 80 years 11.27 (CI 9.96–12.57) Supplementary file2 (DOCX 17 kb)Below is the link to the electronic supplementary material.


The prevalence of incidental H–P lesions in girls with CPP <6 years of age, 6–6.9 years of age, and 7–7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively (p = 0.21). Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged 6–7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in 5 (1.9%) girls with CPP aged of 6–7.9 years. Our findings call into question the routine use of brain MRI in girls with CPP, especially in girls 6 years or older. Current guidelines recommend a follow-up MRI in cases of microadenoma, but few data exist to support this recommendation for children.In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total of 205 age-matched girls with chronic or recurrent headaches without neurological abnormality who had brain MRI were included as controls. The positive MRI findings were categorized as incidental non-hypothalamic–pituitary (H–P), incidental H–P, or pathological. Positive MRI findings were observed in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H–P lesions, 30 (10.2%) as incidental H–P lesions, and 1 (0.3%) as a pathological lesion (tuber cinereum hamartoma). The prevalence of positive MRI findings in girls with CPP did not differ from girls with headaches (13.2% vs. 12.2%,  Central precocious puberty (CPP) is defined as the onset of pubertal signs by the activation of the hypothalamic–pituitary–gonadal axis before 8 years of age in girls and before 9 years of age in boys . CPP is The reported prevalence for unsuspected intracranial lesions in children diagnosed with CPP varies depending on gender, from 8% to 33% in girls . AlthougIntracranial pathology in patients with a common headache occurs at a rate roughly comparable with the general population . TherefoAll girls with CPP who visited the pediatric endocrinology clinic at Inchon St. Mary’s Hospital and Yeouido St. Mary’s Hospital from January 2010 to December 2019 were enrolled in the study. Diagnosis of CPP was made based on the following classic criteria: (1) onset of breast development (stage B2 or above according to the Tanner breast stage) before 8 years of chronological age (CA); (2) advanced bone age at least 1 year over CA; and (3) pubertal luteinizing hormone (LH) response >5 IU/L to a gonadotropin-releasing hormone (GnRH) stimulation test [The clinical data of the girls examined for headache, all of whom were referred to the pediatric neurologic clinic of the two hospitals from January 2010 to December 2019, were reviewed. The subjects chiefly reported experiencing chronic or recurrent headache episodes for 1 month or longer, had a normal neurologic examination, and were between 6 and 8 years of age. Patients with known CNS lesions, prior brain surgery, past history of head trauma, seizure, developmental delay, or associated endocrine disorders, previous hormonal therapies, malformations, or other inherited conditions, including congenital adrenal hyperplasia, were excluded. Among the 3,632 brain MRIs analyzed, 205 cases met the criteria. A total of 205 girls with chronic or recurrent headache 6–7 years of age were included in this study. The CA of the girls at evaluation who had chronic or recurrent headache was 7.0 ± 0.6 years (range 6.0–8.0 years). The study was reviewed and approved by the local Institutional Review Board, which has jurisdiction over the local study populations.The initial evaluation of girls with CPP included height, weight, pubertal maturity, bone age (BA), basal plasma estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels before and after GnRH stimulation. At each evaluation, height was measured using a Harpenden’s stadiometer. Weight and height were recorded to the nearest 0.1 kg and 0.1 cm, respectively. Weight and height SDS were calculated using the 2007 Korean National Growth Charts. Body mass index (BMI) was calculated as weight (kilograms)/height (square meters) and was expressed in SDS for CA, according to the 2007 Korean National Growth Charts . PubertaBrain MRIs were performed before and after gadolinium-enhanced T1- and T2-weighted images in axial, coronal, and sagittal sections, and a GE scanner with a 3.0 Tesla  was used. Thin-section MRI images of the sellar regions (slice thickness of 2.5 mm) were acquired in all patients with CPP, and high-resolution 3D contrast-enhanced MRI images (slice thickness of 1.0 mm) were acquired in all girls with headaches. Dynamic contrast-enhanced imaging of the sellar regions was also acquired in all girls with CPP.For girls 6 years of age or younger who were diagnosed with CPP, a routine sellar MRI was performed. For girls 7 years of age, the sellar MRI was performed when their parents wanted their child to undergo a sellar MRI or if the girls had signs and symptoms suspected of CNS lesions .(1)Normal;(2)(a)incidental: non-hypothalamic–pituitary (non-H–P) or H–P lesions , which are not considered associated with CPP or headache;(b)pathological: lesions known to be the cause of or associated with CPP or headache.Positive:The MRI findings were categorized as follows:p-value <0.05 was considered statistically significant. Categorical variables were expressed as frequencies and percentages, and compared using the Chi-square test or Fisher’s exact test, as appropriate. Continuous variables were expressed as means and standard deviations unless otherwise stated.The data were analyzed using SPSS version 21.0 , and a The CA at pubertal onset in girls diagnosed with CPP was 6.6 ± 0.9 years (range 3.1–7.8 years). Positive MRI findings were found in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H–P lesions, 30 (10.2%) as incidental H–P lesions, and 1 (0.3%) was classified as a pathological lesion. Among the incidental H–P lesions, there were seven cases of Rathke cleft cysts (RCC), six cases of arachnoid cysts, five cases of microadenoma, four cases of pituitary hypoplasia, three cases of cysts of the pars intermedia, three cases of pineal gland cysts, and two cases of pituitary hyperplasia. The only pathological finding was tuber cinereum hamartoma . The patThe CA at evaluation in girls with chronic or recurrent headache was 7.0 ± 0.6 years (range 6.0–8.0 years). The prevalence of positive MRI findings was 25 girls (12.2%) with headache; 12 (5.9%) were classified as incidental non-H–P lesions, 12 (5.9%) as incidental H–P lesion, and 1 (0.5%) was classified as a pathological lesion. Among the incidental H–P lesions, there were seven cases of arachnoid cysts, two cases of microadenoma, two cases of RCC, and one case of pineal gland cyst. The only pathological finding was Moyamoya disease .p = 0.74). There was a trend towards a higher prevalence of incidental H–P lesions in girls with CPP than in girls with headache .The prevalence of positive MRI findings in girls with CPP was not different from girls with headache , 6–6.9 years (n = 148), and 7–7.9 years (n = 114). The prevalence of positive MRI findings was relatively higher in girls with a younger onset, but without statistical significance. The prevalence of incidental H–P lesions in girls with CPP < 6 years of age, 6–6.9 years of age, and 7–7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively  with CPP who had positive MRI findings underwent brain MRI re-evaluation. During the follow-up period (2.2 ± 1.3 years), no lesion showed an increase in size, and signs of neurological or endocrine disorders were not observed in any of the 15 patients. In one patient, the size of microadenoma decreased by 2 mm. Re-evaluation was performed in six girls (50%) with headaches who had incidental H–P lesions, and the size of the pituitary lesions was compared over time; all lesions remained stable.In the present study, the data of 295 girls with CPP obtained from two centers showed that the incidence of pathological lesions in girls with CPP was lower than in previous reports and that the incidence of positive MRI findings in girls with CPP did not differ from girls with headaches. Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged of 6–7.9 years.The findings in the present study showed that a very small portion of girls with CPP (less than 1%) had pathological CNS lesions. Ng et al. reported a high prevalence of neoplasms in CPP girls (15% of 67 subjects) in the United Kingdom between 1990 and 2001 . CisteriFactors contributing to the timing of puberty include obesity, genetic factors involving familial, ethnic, and sex patterns, and environmental factors, such as nutrition and endocrine-disrupting chemicals . In the Our data showed the incidence of positive MRI findings in CPP girls was not different from that in headache girls. There was a trend towards more frequent incidental H–P lesions in girls with CPP than in girls with headaches (10.5% vs. 5.9%). This finding should be cautiously interpreted because different MRI protocols were used between the CPP and headache groups. Despite the high resolution of images acquired in both groups (slice thickness of 1.0–2.5 mm), dynamic contrast-enhanced imaging of the sellar regions was acquired only in girls with CPP. The addition of dynamic images to routine MRI images increases the overall detection rate of pituitary microadenoma . TherefoIn girls with CPP, RCC was the most prevalent incidental H–P lesion, followed by arachnoid cyst and pituitary microadenoma. In girls with headaches, arachnoid cyst was the most prevalent incidental H–P lesion, followed by pituitary microadenoma and RCC. Although RCC has been frequently found in patients with CPP, the relationship between RCC and CPP has not been established yet. A previous study evaluated whether incidentally discovered RCC influences the treatment response of CPP . The autIn this study, microadenomas were detected in 5 (1.9%) of 262 girls with CPP aged 6–7.9 years. The clinical significance of incidental pituitary microadenomas in children is controversial, and there are insufficient data on the long-term outcomes. Pituitary FSH-secreting adenomas were reportedly associated with CPP . In anotArachnoid cysts are incidental findings with a prevalence of 1.7–2.6% in children and in most cases are asymptomatic and found incidentally ,30. PineIn the present study, known pathological lesions were observed in only one (0.3%) girl under 6 years of age. Age <6 years at puberty onset has reportedly been an independent risk factor for pathological CNS lesions in girls with CPP ,33. ReceThe present study had several limitations. First, the retrospective nature of the study does not allow firm causal conclusions to be drawn. Second, the prevalence of brain lesions in girls with CPP who have not undergone brain MRI is unknown, and long-term follow-up of these patients is required.In conclusion, the prevalence of positive findings on brain MRI does not differ between girls with CPP and girls with headaches. Known pathological lesions were rarely detected in CPP girls under 6 years of age and not detected in CPP girls aged 6–7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in five (1.9%) girls with CPP aged of 6–7.9 years. Our data question the routine use of brain MRIs in girls with CPP, especially in girls 6 years or older. Although current guidelines recommend a follow-up MRI in cases of microadenoma, no large studies in children have documented growth of such lesions during follow-up.


The variety of causal agents can make treatment challenging in determining what approach is best suited for the patient’s underlying diagnosis. Trichophyton is a dermatophyte fungus type that is the cause of many cutaneous fungal infections , 2.Treatment of such infections is usually administered by way of topical antifungal creams -5. We re2.th, 2018 with an apparent inflammatory reaction on the plantar surface of both feet (We report a case of a 58-year-old African American male with a long history of scaly itchy feet. The patient presented to the clinic on February 8oth feet  and 2. Aoth feet  and 4. Woth feet  and 6.3.Assessment at 48 hours revealed a Candida 3+ reaction with an induration of 11.5 x 10.8 mm and a Trichophyton 3+ reaction with an induration of 8.5 x 9.2 mm. Based on previous studies conducted using fungal allergens, it is rare to have a 3+ reaction to Trichophyton. Topical treatment with Ketoconazole and 20% Urea creams resulted in complete resolution as noted in


Background: Hypercalcemia is a common electrolyte abnormality presenting with a variety of symptoms. The common causes are primary hyperparathyroidism and malignancy associated with hypercalcemia. However, iatrogenic hypercalcemia with the overzealous use of vitamin D has now emerged as another important cause of hypercalcemia over the past decade.Objective: This study aims to evaluate the causes of hypercalcemia, management strategies, and outcomes in patients admitted with hypercalcemia in a tertiary care hospital.  January 2008 to 31st December 2018. A total of 1142 patients were included in the study and their calcium levels were noted. Along with demographic details, data pertaining to their diagnosis and all investigations done to evaluate the causes of hypercalcemia were noted in a pre-defined questionnaire.Method: It is a retrospective study done at Aga Khan University Hospital (AKUH), Karachi after taking approval from the ethical review committee (ERC). Data were gathered about all patients admitted from 1stResults: A total of 814 patients having hypercalcemia were included in the final analysis and their mean age was 60.8 ± 14.1 years. Male and female patients were 45.4% and 54.6%, respectively, and their mean hospital stay was 6.2 ± 5.8 days. The most common cause of hypercalcemia was malignant solid tumors (49.1%), followed by hematological malignancy (16.5%), hyperparathyroidism (10.9%), definite vitamin D toxicity (8%), chronic kidney disease (4.9%), chronic granulomatous diseases (4.7%), and probable vitamin D toxicity (3.5%). The oral cavity carcinoma (17.7%) was the most common solid tumor associated with hypercalcemia. Amongst hematological malignancy, multiple myeloma (14.4%) was the most common one. Out of 814 patients admitted with hypercalcemia, 601 (74%) patients recovered from hypercalcemia, while mortality was observed in 129 (16%) patients. Of those who expired, 110 (85.3%) had malignancy either solid tumor or hematological.Conclusion: Malignancy is the most common cause of hypercalcemia in admitted patients. The knowledge of hypercalcemia’s causes is of great importance so that targeted investigations can be done. Not only will it minimize the cost burden and shorten the hospitalization of patients; it will also help the physicians to decide the appropriate management accordingly. Moreover, vitamin D toxicity was also observed in a significant number of patients which highlights the common practice of using higher doses of vitamin D by physicians. Hypercalcemia is labeled when serum calcium levels are above the laboratory-specific reference range, i.e. albumin corrected serum calcium >10.5 mg/dL or ionized calcium level >5.52 mg/dL . HoweverThe majority of studies are done to evaluate the presence of hypercalcemia in different diseases. The prevalence of hypercalcemia in solid cancers was found to be 21.92% . SimilarThe parathyroid hormone plays an important role in the mobilization of calcium from bones, reabsorption of calcium from the kidney, and activation of alpha one hydroxylase leading to the formation of the activated form of vitamin D . Activated vitamin D is required for the reabsorption of calcium from the renal tubules and intestine . TherefoIn this study, we will discuss the frequency of different disorders contributing to hypercalcemia. The knowledge of these disorders and their frequency in our region is a need of the present time for the clinicians. It will help to advise appropriately cost-effective investigations and management options and prevent iatrogenic conditions like vitamin D toxicity. We have also looked for the management opted for hypercalcemia and its outcome in our study participants.This is a retrospective study analyzing all the patients admitted to the hospital from 1st January 2008 to 31st December 2018 who had hypercalcemia. It is done in Aga Khan University Hospital (AKUH), Karachi, Pakistan which is a tertiary care hospital. After approval from the ethical review committee (ERC) of AKUH, a list of 1142 patients was generated by the health information and management system (HIMS) department. All the patients who had serum calcium levels  above the normal range were included in the study. A normal range for albumin corrected calcium level was 8.5-10.5 mg/dL and ionized calcium level was 4.8-5.52 mg/dL. At least two abnormal readings were required to label it as a case of hypercalcemia. The demographic details were noted, and the electronic health record was reviewed for the investigations done for evaluation of the etiology of hypercalcemia. This included serum phosphate, serum creatinine, erythrocyte sedimentation rate (ESR), parathyroid hormone (PTH) levels, and 1,25OH vitamin D levels. We also reviewed histopathology, radiological records, and discharge summaries for the diagnosis of disorders like granulomatous disorders, multiple myeloma, or any malignancy. The diagnosis of primary hyperparathyroidism was made when serum PTH levels were raised or inappropriately normal in the presence of hypercalcemia. Definite vitamin D toxicity was considered when the 1,25OH vitamin D levels were > 150 ng/mL [Due to the fact that serum PTHrP and 1,25OH vitamin D levels were not available in our institute, we do not have data about these laboratory values in our study participants. After establishing the etiology of hypercalcemia, we looked for the hospital course of these patients, management strategies opted for hypercalcemia and the response in terms of normalizing serum calcium level. The outcome was noted as discharge or death of the patient. Despite thorough investigations and the extensive review of the hospital record, the patients in whom the cause of hypercalcemia was not obvious were labeled as hypercalcemia of unknown cause. All these data were recorded on a pre-defined questionnaire.Records of 1142 patients admitted to AKUH with hypercalcemia between January 2008 and December 2018 were reviewed as per the inclusion criteria. Out of 1142 patients, 328 (28.7%) patients were excluded because of hypocalcemia (15 patients), normocalcemia (112 patients), transient hypercalcemia (61 patients), iatrogenic hypercalcemia (3 patients), idiopathic (48 patients), and incomplete workup (89 patients). The electronic health records of the remaining 814 (71.3%) patients were reviewed and analyzed.Out of 814 hypercalcemia patients, 370 (45.4%) were males and 444 (54.6%) were females with the mean age of 60.8 ± 14.1 years. The mean hospital length of stay was 6.2 ± 5.8 days. The length of stay was less than four days in 398 (48.9%) patients and more than equal to four days in 51.1% of patients. Patients with different levels of 1,25OH vitamin D and PTH are characterized in Table Calcium levels were not normalized in 273 (33.5%) patients despite all standard treatment options whereas, 22.4% of patient’s calcium levels were normalized in less than three days, 29.6% in three to five days, 12.3% in five to ten days, and 2.2% were normalized in more than 10 days  accompanied by hematological malignancy (16.5%), hyperparathyroidism (10.9%), definite vitamin D toxicity (8%), chronic kidney disease (4.9%), chronic granulomatous disease (4.7%), and probable vitamin D toxicity (3.5%) Table . Among solid tumor malignancy, oral cavity (17.7%) was the most common followed by breast carcinoma (14.7%), lung carcinoma (8.8%), and 5.8% of patients suffered metastatic tumor with unknown primary. In patients with hematological malignancy, the most common malignancy was multiple myeloma (14.4%) followed by non-Hodgkin lymphoma (7.4%), Hodgkin lymphoma (1.5%), chronic lymphocytic leukemia (CLL) (0.9%), chronic myeloid leukemia (CML) (0.2%), and acute myeloid leukemia (AML) (0.2%) Table .Out of 814 patients, 601 (74%) patients recovered from hypercalcemia during the hospital stay and were sent back home, 59 (7.3%) patients left against medical advice (LAMA), 25 (3%) underwent parathyroidectomy, and 129 (16%) patients expired  patients had low PTH levels, 11 (27.5%) had normal PTH levels, and 15 (37.5%) had high PTH levels. Out of 814 patients with hypercalcemia, 13 patients underwent hemodialysis due to their underlying end stage renal disease (ESRD), but not due to hypercalcemia. Reasons of hospitalization in our hypercalcemia patients were drowsiness, reduced oral intake requiring IV fluids administration, vomiting, and extreme lethargy. The most common cause of hypercalcemia in our study was found to be malignant solid tumor followed by hematological malignancy. In one study published in 2018, malignancy was the leading cause of hypercalcemia in hospitalized patients (54%-65%) . HypercaThe most prevalent malignant solid tumor in our study was oral cavity carcinoma (17.7%) followed by breast (14.7%) and lung carcinomas (8.8%). The increased incidence of oral cavity carcinoma in our population is because of the increased use of tobacco and betel nuts in all age groups and in both genders. In one study, the common tumors associated with humoral hypercalcemia of malignancy were squamous cell carcinomas of the lung, head and neck cancers, esophagus, skin, cervix, breast, kidney, prostate, or bladder cancers . AccordiJournal of Leukemia and Lymphoma, the presence of hypercalcemia in patients with newly diagnosed diffuse large B cell lymphoma was found to be 18% [Annals of Intensive Care in 2019, the hematological malignancies were the contributing cause of hypercalcemia in 44.3% of patients [The hematological malignancy was the second most common cause of hypercalcemia in our study. The most common malignancies contributing in this group were multiple myeloma in 82 patients 14.4%), followed by Non-Hodgkin lymphoma in 42 patients (7.4%). In one study published in the o be 18% . In a st.4%, follHyperparathyroidism is the third common cause accounting for 10.9% of hypercalcemia in our study. With widespread testing for calcium levels being done these days, primary hyperparathyroidism is now commonly diagnosed in an asymptomatic phase. It is the most frequent etiology of hypercalcemia in the outpatient population . In our Vitamin D toxicity is the fourth common contributor of hypercalcemia in our study. Vitamin D toxicity is diagnosed by serum levels of vitamin D3 above 150 ng/mL. It is characterized by severe hypercalcemia and low or undetectable PTH hormone levels . In our Annals of Intensive Care in November 2019 in which out of 131 patients with hypercalcemia, 124 patients (94.6%) received IV fluids, 103 (78.6%) received bisphosphonates particularly those with solid tumor and hematological malignancies, 65 (50%) patients received corticosteroids, 12 patients (9%) received calcitonin, and none of the patients received denosumab. Out of those patients who received corticosteroids 84.4% of patients had a diagnosis of hematological malignancy [In our study, the treatment options used to treat hypercalcemia were bisphosphonates (77.5%) followed by steroids (38.8%) and calcitonin (17.9%) in order of frequency. Denosumab was not available at the time of our study period. In our study in the hematological malignancy group, 69 patients (51.8%) received steroids. This data is comparable to one study published in the lignancy . In anotThe workup of hypercalcemia was incomplete in 89 (8.7%) patients. Because of the retrospective nature of the study, it was difficult to label a definite diagnosis in these patients. Transient hypercalcemia was labeled where serum calcium levels normalized within the first 24 hours and it was observed in 61 patients (6%). In 48 (4.73%) patients no cause of hypercalcemia was found, despite the extensive standard workup of hypercalcemia. Other causes of hypercalcemia in our study include chronic kidney disease in 40 patients (4.9%) and chronic granulomatous diseases in 38 patients (4.7%) (including mainly tuberculosis and sarcoidosis).The majority of the participants 73.8% (601) had normalization of serum calcium levels and were discharged home, while 15.8% (129) were expired either due to complications related to hypercalcemia or primary disorder. The majority of the patients who expired had primary disorder as malignancy, i.e. 93 patients had solid tumor malignancy and 18 patients had hematological malignancy.Appropriate identification of underlying diagnosis and treatment of hypercalcemia is very essential in limiting morbidity and mortality associated with this entity, prolonged length of hospital stay, and economical burden on patient’s family . History of vitamin D intake should be taken very vigilantly. Physicians should avoid overzealous replacement of vitamin D as it is the need of time to avoid vitamin D toxicity; in order to do so, they should review recommendations from the guidelines of the Endocrine Society in the management of vitamin D deficiency.


To evaluate the effect of topical cyclosporine A (CsA)  on recurrence rates and tear metrics after pterygium excision and limbal-conjunctival autografting (LCUA) technique in patients with primary pterygium.A total of 60 eyes of 60 patients with primary pterygium who underwent pterygium excision and the LCUA technique were evaluated prospectively. Among them, 30 eyes of 30 patients were treated with topical CsA (Restasis) for 6 months postoperatively (Group 1). The remainder of the patients were assigned to Group 2. The follow-up period was 12 months for each group. The primary outcome measures were a comparison of Schirmer I test and fluorescein tear break-up time (FTBUT) results, the recurrence rate, and postoperative complications.There were no significant differences in age  or sex between groups (p>0.05). Farmers were the largest group of patients (40.0%). Recurrence of pterygium was observed in 5 (16.6%) eyes in Group 1 and 8 (26.6%) eyes in Group 2. The recurrence rate was not statistically significant between groups (p=0.35). The complication rate was significantly lower in Group 1 compared with that of Group 2 (p=0.02). The average increase in Schirmer I and FTBUT values was significantly higher in Group 1 than in Group 2 (p<0.05).The use of topical CsA did not demonstrate any significant improvement in the recurrence rate of pterygium following LCUA surgery. Pterygium is one of the most common ocular surface diseases associated with neovascularization and inflammation . The majCyclosporine A (CsA) is an immunosuppressive agent that selectively inhibits T-helper cells and prohibits the expression of pro-inflammatory cytokines . In addiVarious methods are available for the investigation of DES. Among these Schirmer test or fluorescein break up-take time (FTBUT) have been used in several studies to investigate the relationship between pterygium and DES with conflicting results. In this study, we investigated the effectiveness of topical CsA on the patients who underwent pterygium excision with limbal-conjunctival autografting (LCAU) and then compare the incidence of recurrence in pterygium after the surgery for the treatment and control groups.In this prospective study, 60 eyes of 60 patients with primary pterygium who underwent pterygium excision using the LCAU technique were included in the study. The patients were randomly divided into two groups (Group 1 and Group 2), both including 30 eyes of 30 patients. All the included patients had primary nasal pterygium exceeding 2 mm , ocular irritation resistant to medical treatment, and decreased visual acuity associated to the pterygium. Exclusion criteria were recurrent and atrophic pterygium, topical CsA allergy, history of the lid or ocular diseases, use of systemic or local medication, and pregnancy.®, Allergan Pharmaceutical) was given to Group 1, with 6-h periods in a day during the postoperative 6 months. In Group 2, patients did not receive CsA.One experienced surgeon performed all surgeries (ASK). Under local anesthesia with 0.5% proparacaine hydrochloride, the pterygium head was removed from the cornea with a scalpel; then, together with Tenon’s capsule, the pterygium was dissected with Westcott scissor. In cases of bleeding, cauterization was avoided in order to prevent any damage to the limbal area. Under the supratemporal bulbar conjunctiva, 0.25 ml of normal saline was injected, and a piece of the conjunctiva, equal in size to the bare area left at the site of the excised pterygium, was marked from the limbal region and removed from Tenon’s capsule. We performed a superficial circumferential incision 0.5-mm from the superotemporal limbus to include limbal epithelium in the conjunctival graft. This piece of the conjunctiva was then sutured, with a continuous 10/0 nylon suture, to the bare area. The region where the conjunctival autograft was taken from was left for primary healing. All the patients received topical antibiotic (moxifloxacine) four times daily for 2 weeks, and topical steroids (dexamethasone) four times daily for a month. Topical 0.05% CsA  software . The data were not normally distributed, met by the Kolmogorov–Smirnov test (p<0.05). Quantitative data were compared by Mann–Whitney U and Wilcoxon Signed Ranks Test tests. Kaplan–Meier survival analysis was performed to determine the recurrence-free survival time. Chi-square test was used to investigate the categorical data. P-value <0.05 were considered to be statistically significant.The mean age of Group 1 and 2 was 55.0±9.7 and 56.3±8.9 years, respectively (p=0.54). A total of 14 (46.6%) of the patients in the treatment group were male; 16 (53.3%) of the patients in the control group were male (p=0.45). The mean follow-up period for Group 1 was 11.6±3.4 months  and 12.7±3.2 months  for Group 2 (p=0.21). A total of 24 (40.0%) of the patients included in our study were farmers, 13 of whom were Group 1, and the reminder in Group 2. A total of 23 (38.3%) were housewives, 13 (21.6%) were civil servants.In Group 1, the mean preoperative Schirmer I and FTBUT values were 7.9±2.6 mm and 7.7±2.0 s. At the end of the follow-up period, these were 12.3±1.9 mm and 13.7±1.9 s, respectively. In Group 2, the mean preoperative Schirmer I and FTBUT values of Group 1 were 10.6±2.5 mm and 10.0±3.3 s. At the last visit, these were 13.5±2.8 mm and 12.9±3.0 s, respectively. The mean postoperative Schirmer I and FTBUT were not significantly different between groups (p>0.05). However, when pre-and post-operative Schirmer I and FTBUT values were compared, the average increase was significantly higher in Group 1 (p<0.05) .In the early postoperative period, all patients in the two groups had symptomatic complaints of ocular pain, photophobia, lacrimation, and sensation of a foreign body in the eye. No adverse effect was observed in patients receiving topical CsA except a mild irritation when the drug was applied. Punctate corneal staining was not detected in Group 1. No serious complication has been detected in any of the cases in our study.The only postoperative complication in our study was Dellen formation. This complication was significantly higher in Group 2  compared to Group 1  (p=0.02). The Dellen formation was healed after treatment with preservative-free eye drops within 1 week.The mean recurrence time was 2.40±1.16 months in Group 1 and 3.00±0.70 months in Group 2. Recurrence of pterygium was observed in 5 (16.6%) eyes in Group 1 and 8 (26.6%) eyes in Group 2. The risk of pterygium recurrence was 1.6 times higher in Group 2 than in Group 1 . However, the difference was not statistically significant between groups (p=0.57).The treatment for pterygium is surgical excision. Although bare sclera excision is a simple approach, recurrence is the most common complication. However, there is no definitive treatment modality that prevents postoperative recurrence as well as associated complications.A previous research demonstrated that pterygium is a local deficit of limbus . The degAdjuvant agents are treatment choices that help to eliminate recurrence after surgery. Mitomycin C (MMC) is the most commonly used adjuvant agent that prevents cellular activity by inhibiting DNA synthesis . It has The CsA is anti-inflammatory drug that has been widely applied topically in ocular surface diseases -13. PrevSeveral studies evaluated the use of topical CsA to prevent recurrences following pterygium excision  18, 28- They fouAlthough the association between DES and pterygium is unclear, some studies suggested that the alteration of tear film layer may induce the proliferation subconjunctival fibrovascular tissue. Gunduz et al.  reportedIn our study, we aimed to evaluate whether the use of topical CsA following pterygium surgery has any effect on Schirmer I and FTBUT test results which may be the indicators of DES. Postoperatively, these values were not significantly different between groups however, the average increase in these values was significantly higher in Group 1. Although the patients treated with topical CsA did not show any significant recurrence rates, topical CsA may help to correct tear film layer irregularities and consequently treats DES following pterygium surgery which contributes to decrement of recurrence rates in addition to its anti-inflammatory effect.The CsA 0.5% formulation twice a day dosing was approved for clinical use based on the phase 3 studies. The ocular retention time of this formulation was approximately 2 h hence a more frequent dosing might be necessary in cases with severe dry eye or ocular surface disorders to control the inflammation more effectively , 34. In Dellen was the main postoperative complication in the current study. This may be explained by corneal irregularity due to decreased Schirmer I results in the early postoperative period. These patients were successfully treated with preservative-free eye drops.This study has some limitations. First is the small sample size. Second is the short follow-up period. Third is the lack of pterygium size information since higher level of corneal involvement is correlated with higher recurrences. Finally, there was no placebo treatment for Group 2.In conclusion, topical CsA did not show any significant improvement in the recurrence rate of pterygium following LCAU surgery. Our findings should be evaluated in future prospective studies including a larger population in a long follow-up period.Adiyaman University Faculty of Medicine Biomedical Research Ethics Committee, protocol number: 2015/1-9, Date: 25/01/2015.Externally peer-reviewed.None declared.Involved in design and conduct of the study ; preparation and review of the study ; data collection ; and statistical analysis .


The COVID-19 pandemic is a major public health problem. Subsequently, emergency medical services (EMS) have anecdotally experienced fluctuations in demand, with reports across Canada of both increased and decreased demand. Our primary objective was to assess the effect of the COVID-19 pandemic on call volumes for several determinants in Niagara Region EMS. Our secondary objective was to assess changes in paramedic-assigned patient acuity scores as determined using the Canadian Triage and Acuity Scale (CTAS).We analyzed data from a regional EMS database related to call type, volume, and patient acuity for January to May 2016–2020. We used statistical methods to assess differences in EMS calls between 2016 and 2019 and 2020.A total of 114,507 EMS calls were made for the period of January 1 to May 26 between 2016 and 2020, inclusive. Overall, the incidence rate of EMS calls significantly decreased in 2020 compared to the total EMS calls in 2016–2019. Motor vehicle collisions decreased in 2020 relative to 2016–2019 (17%), while overdoses relatively increased (70%) in 2020 compared to 2016–2019. Calls for patients assigned a higher acuity score increased (CTAS 1) (4.1% vs. 2.9%).We confirmed that overall, EMS calls have decreased since the emergence of COVID-19. However, this effect on call volume was not consistent across all call determinants, as some call types rose while others decreased. These findings indicate that COVID-19 may have led to actual changes in emergency medical service demand and will be of interest to other services planning for future pandemics or further waves of COVID-19. The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a major public health problem. The first case of COVID-19 in Canada was documented on January 25th, 2020 in Ontario . These aVolumes of EMS calls are important to understand since they impact the response times, and are part of quality of EMS care . FluctuaNEMS is a large service that, in June of 2016, had approximately 3.9% of Ontario’s EMS call volumes . NiagaraA cross-sectional analysis of de-identified data obtained from the NEMS database (EDGE) was conducted. Electronic Patient Care Record (ePCR) data for each patient was extracted from the database. A time period of January 1 to  May 26, 2020 only was chosen to reflect the onset and establishment phases of the pandemic. Further data from the same time period from 2016 to 2019 were extracted. These time periods were chosen to be comparable due to seasonal variation in EMS calls at the daily, monthly, and yearly level [2 that comprise the Niagara Region of Ontario [NEMS serves 12 municipalities and 1850 km Ontario . As of t Ontario .The NEMS ambulance communications center utilizes the Medical Priority Dispatch System (MPDS®) to categorize and triage calls coming into the center. Paramedic service data from both land ambulance and dispatch were accessed through a business intelligence solutions product called SAP Business Objects Edge Edition’ EDGE . InformaEMS calls were reported as counts and were stratified by call determinant type . We examined changes in patient acuity levels from January 1 2019 to May 26 2020. Patient acuity was measured through the Canadian Triage and Acuity Scale (CTAS), a validated 5-level triage score used by paramedics on scene arrival . Level 1t is the population size in 2019, o represent 2019 and 2017, respectively.o represent 2020 (and 2018) and 2017, respectively.The total number of EMS calls were tabulated for each determinant and year, and then summed for the time period of 2016–2019. Chi-square tests of independence were conducted to compare the proportion of EMS calls in 2020 to EMS calls in 2016–2019 for each call determinant. Fisher’s exact test was used for determinants with frequencies of 5 EMS calls or less. We also conducted a chi-square test of independence to compare the incidence rate ratios of EMS calls in 2020 to 2016–2019. Using population data for 2016, 2017, and 2019 in the Niagara region estimated by Statistics Canada , we madeWe used these projections to calculate the incidence rate ratios of EMS calls in 2016–2019 and in 2020, with person-years as the denominator and number of EMS calls as the numerator.st, 2019 to May 26th, 2020 using chi-square tests of independence to compare total calls in 2016–2019 to the total calls in 2020.Changes in patient acuity were assessed for the timeframe of January 1Data were analyzed in RStudio desktop version 1.2.50331 using R version 3.6.1 .A total of 114,507 EMS calls were made to NEMS for the period of January 1 to May 26 between 2016 and 2020, inclusive  for cardiac arrest (1.8% versus 1.4%), heart problems (1.9% versus 1.7%), overdose/poisoning (4.4% versus 2.6%), pregnancy (0.5% versus 0.4%), stroke (3.3% versus 2.9%), and unconscious (9.7% versus 8.6%); see Table Several types of EMS calls increased during January–May 2020 when compared to the same time frame in 2016–2019. Niagara had its first COVID-19 case on March 13p < 0.05) in 2020 for breathing problems (10.2% versus 11.5%), carbon monoxide/HAZMAT (0.2% versus 0.3%), choking (0.2% versus 0.3%), chest pain (8.8% versus 9.0%), diabetic (0.9% versus 1.2%), sick person (11.3% versus 18.3%), motor vehicle collision (3.2% versus 3.8%), and unknown problem (4.1% versus 5.1%).However, compared to 2016–2019, EMS calls significantly decreased (p < 0.01) than EMS calls for the same time-period in 2016–2019 (0.046 versus 0.049); see Table The incidence rate of EMS calls in Niagara 2020 was significantly lower (p < 0.01) for calls assigned a CTAS level of 1 (4.0% versus 2.9%) and for CTAS level 4 (14.3% versus 12.3%); see Table p < 0.01) for calls assigned a CTAS level of 2 (22.9% versus 24.3%) and CTAS level 3 (78.4% versus 94.1%).EMS calls significantly increased  decreased the most. People may have been commuting and travelling less frequently and had been encouraged to stay at home, therefore were less likely to become involved in car accidents. A study in Michigan, USA, examining the effect of shelter-in-place orders on orthopaedic trauma, also found that motor vehicle collisions decreased by 17% in March 2020 relative to March 2019 . AlthougThe number of patients presenting as high acuity (CTAS Level 1) and lower acuity (CTAS level 4) increased during the pandemic. A possible explanation for this is that lower acuity patients are not seeking care in time, so that when EMS is called they present as high acuity . HoweverWe cannot solely attribute the decrease in EMS calls to the COVID-19 pandemic. EMS calls could also have decreased due to changes at dispatch because of an MPDS system upgrade that was implemented in 2019. Additionally, in the same year the triage process was changed for certain conditions, a Mobile Integrated Health Team, with additional mental health training, may have been dispatched instead of a regular ambulance. The decrease in EMS calls may also be attributed to the lack of tourists in attendance in the region, which typically accounts for a portion of the Niagara EMS calls each year. The population of Niagara has 13 million visitors each year, and a decrease in visitors may lead to a decrease in 9-1-1 calls . Though We have confirmed that overall, EMS calls in the Niagara region have significantly decreased during the first 5 months of the COVID-19 pandemic, whilst some types increased. Specifically, EMS calls for overdose increased the most out of any other call determinant, while calls for motor vehicle collisions decreased more than any other determinant. Calls related to high patient acuity levels significantly increased, while EMS calls for urgent and emergent patients significantly decreased. Our findings suggest that the COVID-19 pandemic could have contributed to a decrease in EMS calls overall, and increased certain types of calls, including an increase in the number of high acuity patients. The results of this study may be generalizable to other geographical areas with similar population sizes and characteristics but may not be generalizable to areas that don’t provide universal healthcare. These findings may be of interest to other EMS as they plan for future pandemics or second waves of COVID-19, including the ability to predict call type in an effort to adjust a targeted response. This information can also provide an opportunity for dialogue between EMS agencies and health care partners on the consequences of delays in seeking treatment.


WBC , NEU , RDW , and PT  also had accuracy for complications prediction. RDW had a good ability to predict heart failure in NSTEMI patients . An acceptable ability to predict ventricular rhythm disturbances occurrence had WBC  and NEU . Hematological and coagulation parameters can help in risk stratification of ACS patients. RDW, WBC, NEU, and PT were able to predict mortality and in-hospital complications in ACS patients. RDW has a good accuracy in predicting complications and heart failure in NSTEMI patients. WBC and NEU are good predictors for ventricular rhythm disturbances.The values of hematological and coagulation biomarkers were evaluated as predictors of in hospital mortality and complications, in patients with acute coronary syndromes (ACS). This retrospective observational study enrolled 936 ACS subjects admitted to the Clinical Emergency Hospital of Oradea, Romania, between January–December 2019. Hematological and coagulation parameters were obtained at admission. During hospitalization, the following adverse events were recorded: death, ventricular rhythm disturbances, atrial fibrillation, heart failure, re-infarction, and stroke. Accuracy of hematological and coagulation parameters as predictors of adverse outcome were also evaluated. The diagnosis was unstable angina in 442 patients (47.22%), non-ST-elevation myocardial infarction (NSTEMI) in 113 patients (12.1%) and ST-elevation myocardial infarction (STEMI) in 381 patients (40.70%); 87 patients (9.29%) died during hospitalization and 193 (20.7%) developed complications. Predictors for in hospital mortality were as follows: red cell distribution width (RDW) (AUC 0.691,  Coronary artery disease (CAD) is the leading cause of death worldwide and is most commonly the result of atherosclerosis. Atherosclerosis is a systemic inflammatory disease, and inflammation plays an important role in the pathophysiology of acute coronary syndromes (ACS). There is a persistent low-grade inflammation that contributes to the initiation and progression of the atherosclerotic process. Atherosclerosis plaques may become unstable leading to thrombosis and development of ACS. Acute coronary syndrome (ACS), including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), is one of the most frequent reasons for hospital admission .Despite the use of guideline recommended therapies including early percutaneous coronary intervention (PCI) the prognosis in ACS is still poor and therefore early risk stratification is needed ,3.The inflammation associated with ACS leads to increase research in the field of new inflammatory biomarkers that are useful in the diagnosis and risk stratification of patients. In acute myocardial infarction (MI) there is an increased myeloid activity , and theIn recent years, strong interest was present regarding these parameters, many studies proved their prognostic value for mortality, major cardiovascular events, rhythm disturbances, and stent thrombosis in ACS, while in other studies the results are contradicting their outcome prediction potential. Further studies on these hematological biomarkers are necessary. For example, white blood cell count (WBC) was found to be an important predictor for death in the first 30 days to 6 months following acute MI . NeutropThe aim of this study was to evaluate the value of hematological and coagulation biomarkers as predictors of in-hospital mortality and complications in patients admitted for ACS in a north-western hospital in Romania. The data obtained through this exhaustive research  provide valuable information to clinicians in order to better conduct the risk stratification of patients with ACS.A retrospective observational study was performed on 936 patients consecutively admitted with the diagnosis of ACS in the Cardiology Department of the Clinical County Emergency Hospital of Oradea, Romania. Inclusion criteria was the diagnosis of ACS.The selection and inclusion-exclusion criteria of the patients are presented in the flow chart .All the patients had CBC blood sample analysis performed at admission. Coagulation tests were missing in 43 patients. Ejection fraction was not registered in 21 patients. Patients with missing data were mainly in the group with unstable angina.The following adverse events were recorded during hospitalization period: death and other major complications like ventricular rhythm disturbances, development of acute MI for patients with unstable angina (UA) or re infarction, heart failure, new onset atrial fibrillation, and stroke. Hematological and coagulation parameter obtained at admission were compared between groups of patients with/without adverse events, and those parameters that differed significantly between groups were evaluated regarding their predictive accuracy.ACS consisted of: UA, NSTEMI, and STEMI. The diagnosis of UA was defined in the presence of acute chest discomfort described as chest pain or chest pain equivalent symptoms (dyspnea) and ECG changes indicating myocardial ischemia: persistent or transient ST depression, T wave inversion, flat T waves, pseudonormalization of T waves, without evidence of cardiomyocyte necrosis, respectively with normal high-sensitivity cardiac troponin I value . NSTEMI Data were obtained from patient’s medical records and from hospital informatic system. Demographic data, medical history, clinical and paraclinical data, and risk factors were recorded.Hematological parameters were assessed at admission by using CELL-DYN Ruby System , an automated hematology analyzer that perform cell by cell analysis from a single sample dilution to count and differentiate white blood cells using Multi-Angle Polarized Scatter Separation (MAPSS) technology. The device also uses optical laser light scatter analysis, without the need to reflex to another test mode, to provide both the red blood cell and platelet counts. Coagulation tests performed at admission were registered: prothrombin time (PT) and activated partial thromboplastin time (APTT). For this purpose, it was used ACL TOP Family 500 CTS .Atrial fibrillation was defined as heart rhythm with no discernible P waves and irregular RR intervals lasting at least 30 s . VentricHeart failure was appreciated by corroborating clinical signs with echocardiographic data. Left ventricular ejection fraction was appreciated with Simpson s method, recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging .Stroke was diagnosed based on neurological evaluation and cerebral computed tomography scanning. Re-infarction was defined as an acute MI that appeared after the incident Mi and was manifest as reappearance of ischemic symptoms associated with new ST elevation or new pathognomonic Q waves in at least two contiguous leads and confirmed by high sensitivity troponin assays (two samples at 3–6 h apart). If the initial value was elevated but stable or decreasing, the second troponin value required a >20% increasing, if the initial value was normal than criteria for new acute MI apply .t-test for continuous variables and Kruskal–Wallis test for categorical variable. A value of p < 0.05 was considered statistically significant.Data were analyzed using SPSS statistical package version 25 and MedCalc statistical software. Results are presented as mean ± SD for continuous variable and frequencies and percentage for categorical variables. Intergroup comparison was made using independent sample For those hematological and coagulation parameters that were significantly different between various groups a ROC curve analysis was performed with determination of AUC (area under curve) to evaluate the accuracy or the performance of these parameters in predicting mortality or adverse outcome. Optimal cutoff value with highest Youden index was determined for each parameterDemographic data , clinical  and paraclinical variables  that were statistically significant different between various groups were included in a multiple regression analysis in order to evaluate the independent predictive value for each parameter. In order to evaluate the independent predictive value for mortality, the multivariate Cox regression analysis was performed.The diagnosis was unstable angina in 442 patients (47.22%), NSTEMI in 113 patients (12.1%), and STEMI in 381 patients (40.70%). Mean age was 65.64 ± 11.794 years and 64.1% were male. Coronary angiography was performed in 720 patients (76.9%) and 490 (52.4%) patients with suitable anatomy were treated with interventional revascularization. The rest of the patients were sent to coronary artery bypass  or had nonsignificant (<50%) coronary artery stenosis. A number of 625 patients (66.8%) were hypertensive, 424 patients were with dyslipidemia (45.3%), 294 patients (31.4%) had diabetes, and 224 patients were smokers (23.9%). Duration of hospitalization was 5.6 ± 4.92 days.The mortality rate during hospitalization was 9.29% (87 patients). Comparison of baseline characteristics: clinical and paraclinical features in patients discharged alive and deceased are represented in p < 0.001), WBC , and NEU . A cut off value of 12.5 g/dL for HGB has a sensitivity of 49.4% and a specificity of 79.6% in identifying patients at risk of death. A cut off value of 15.36 × 10³/μL for WBC can identify with a sensitivity of 43.2% and a specificity of 88.9% a higher risk of mortality. NEU value higher than 8.3 × 10³/μL has a sensitivity of 64% and a specificity of 69.2% in predicting mortality. NLR had an AUC of 0.626, 95% CI 0.594–0.656, (p = 0.008), and a value >5.116 indicates with a sensitivity of 48.28% and a specificity of 81.23% mortality risk. RDW was also able to predict mortality with an AUC 0.691, 95% CI 0.656–0.724, (p < 0.001) and with a cut off value of 12.48% having a sensitivity of 67.1% and a specificity of 66.7% for detecting patients with high risk of mortality.The following hematological parameters had discriminative power in predicting mortality: hemoglobin (HGB) . A cut off value of 14.95 s for PT has a sensitivity of 64.8% and a specificity of 80.1% in detecting patients with higher risk of death. The comparative value of the parameters as predictors of mortality in ACS patients is revealed in Better discriminative power was registered for PT . Other independent predictors of death were: LVEF , creatinine , diagnosis of STEMI , and age .In multivariate Cox regression analysis WBC remained independent predictors of mortality  and the discriminative power of this parameter was good , with a cut off value of 163.625 (sensitivity 100% and 87.9% specificity) indicating a group of patients at high risk of death, but there only three patients with UA in the mortality group.For the patients with diagnosis of UA, PLR was significantly higher in the mortality group . A cut off value of 15.36 × 10³/μL can identify with a sensitivity of 63.6% and a specificity of 87.3% patients with high risk of mortality. RDW was also significantly higher in the mortality group and had an acceptable discrimination power . A value of more than 12.73% can identify with a sensitivity of 72.7% and a specificity of 68.1% patients with increased risk of death.Thirteen patients with diagnosis of NSTEMI died during hospitalization period. In these patients, WBC were significantly higher  with a fp < 0.001), and a cut off value of 14.9 s can indicate with a sensitivity of 62.22% and a specificity of 90.32% a higher risk for death. RDW was significantly higher in the mortality group in STEMI patients with a fair discriminative power . A cut off value of 12.51% has 66.7% sensitivity and 72.1% specificity in detecting high risk of mortality.A number of 71 deaths were registered among patients with STEMI. Coagulation parameter PT was significantly higher in the mortality group . This pap = 0.004) and PLR 169.23 ± 163.28 vs. 122.388 ± 71.15 (p = 0.02). NLR  and PLR  failed in predicting death in patients with PCI.From ACS patients treated with PCI and stenting a number of 18 patients died. Deceased patients treated with interventional revascularization had significantly higher NLR 6.38 ± 7.02 vs. 3.66 ± 3.72 (A number of 193 patients (20.7%) developed complications during hospitalization. Atrial fibrillation occurred in 35 patients (3.7%), ventricular rhythm disturbances appeared in 56 patients (6%), 116 patients developed heart failure (12.4%), 15 patients (1.6%) had a new myocardial ischemic event (MI or re infarction) and 7 patients (0.7%) developed ischemic stroke. A number of 26 patients (2.77%) developed more than one complication. Comparative clinical and paraclinical parameters in patients with and without in-hospital complications are shown in p < 0.001), NEU , RDW  were found to have ability for complications prediction. NLR had very poor discriminative value for complications . Cut off values of 13.92 × 10³/μL for leucocyte  can identify patients predisposed to complications. For NEU a cut off value of 6.82 × 10³/ μL can identify complication predisposed patients with a sensitivity of 67.5% and a specificity of 59.1%. Moreover, WBC persists as independent predictor for complications in ACS patients after multiple regression analysis .WBC . Other independent predictors were as follows: age , LVEF , creatinine , diagnosis of STEMI .RDW had a cut off value of 12.53%  and NLR had a cut of value of 4.39  for complication prediction. In addition, RDW was an independent predictor of complications in a multivariate regression analysis  and a value lower than 13.64 g/dL has a sensitivity of 59.6% and a specificity of 60% for complication detection. Another parameter that can predict complications was found to be PT  with a cut off value of 14.4 s . The best hematological parameters predictors of complications are revealed in HGB had also an ability in predicting complications . The AUC was 0.669, 95% CI 0.614–0.722, (p = 0.0016) and RDW value of more than 13.14% can identify with a sensitivity of 46.3% and a specificity of 82.37% complications risk.A number of 43 patients with UA developed complications. In these patients, RDW was significantly increased . A cut off value of 6.13 × 10³/μL for NEU can identify with a sensitivity of 85% and a specificity of 53.2% the patients who will develop complications. WBC had a cut off value off 14.38 × 10³/μL that can identify with a sensitivity of 55% and a specificity of 83.9% the patients predisposed to complications.There were 30 patients among those with diagnosis of NSTEMI that developed complications. NEU and WBC were significantly higher in patients with NSTEMI  who devep = 0.001) with a cut off value of 14.04% .RDW had a fair discriminative value for complications in patients with NSTEMI . A value lower than 13.4 g/dL had a sensitivity of 56.7% and a specificity of 72.4% for complication prediction. Acceptable discriminative power for complications occurrence was found also for PT , with a cut of value of 14.7 s .HGB was significantly lower in the group of patients with complicated STEMI  and had p < 0.001) with a cut off value 12.51% .RDW is also able to detect complications prone STEMI patients  and fail to identify patients at risk of complications. WBC  with a value higher than 14.6 × 10³/μL is correlated with risk of complications with a sensitivity of 45.4% and a specificity of 77.9%. NEU  with a value higher than 13.56 × 10³/μL can be correlated with complications with a sensitivity of 33% and a specificity of 88.8%. The accuracy of WBC and NEU for complication prediction in STEMI patients was poor.WBC, NEU, and NLR were significantly higher in STEMI patients that developed complications. NLR had an AUC of 0.599, 95% CI 0.499–0.601, (p < 0.001). A value over 14.7 s has a sensitivity of 42.17% and a specificity of 89.39% for predicting complications. As well, PT persisted as independent predictor of complications in STEMI patients after multiple regression analysis . Other independent predictors were LVEF , age , and creatinine .PT was significantly increased in patients with complicated STEMI, and had an acceptable discriminative power  with a cut off value of 11.92% .A number of 86 ACS patients treated with interventional revascularization therapy developed in-hospital complications. RDW was significantly higher in stented patients that developed complications . The AUCp = 0.001). A cut of value of 14.7 s can discriminate with a sensitivity of 35.7% and a specificity of 89.6% patients treated with interventional revascularization and stenting that are at risk for complications.PT was also significantly higher in patients treated with PCI that developed complications and had an AUC 0.638 , NEU  and HGB  were significantly higher in stented patients who developed complications but had a poor discriminative power for complications in patients treated with interventional revascularization therapy. NLR  and PLR  were higher in the complications group but fail to identify patients at risk for complications.WBC , PLR (p = 0.01), NLR (p < 0.001), NEU (p < 0.001), WBC (p < 0.001), and RDW (p < 0.001) were significantly higher in the group of patients with ACS that developed ventricular rhythm disturbances (HGB level was significantly lower (urbances .p < 0.001) and NEU . A cut off value for WBC of 9.94 × 10³/μL can indicate risk of ventricular arrhythmias with a sensitivity of 85.7% and a specificity of 54.6%. NEU with a value over 7.784 × 10³/μL is associated with ventricular rhythm disturbances with a sensitivity of 79.59% and a specificity of 64.95%.An acceptable ability to predict ventricular rhythm disturbances occurrence in ACS patients had WBC  and HGB  had also discriminative power to detect ventricular rhythm disturbances. The cut off value of 4.25 for NLR is correlated with ventricular rhythm disturbances with a sensitivity of 60.7% and a specificity of 73.6%. A HGB level lower than 12.8 g/dL can detect with a sensitivity of 48.2% and a specificity of 74.1% the risk of ventricular rhythm disturbances in ACS patients.NLR  LVEF .RDW had also an AUC 0.691, 95% CI 0.656–0.724, p = 0.14) and failed regarding ability to identify patients at risk for ventricular rhythm disturbances. The best accuracy in predicting ventricular rhythm disturbances in ACS patients was found for WBC and NEU.PLR had an AUC of 0.573,  but only 2 patients developed severe ventricular arrhythmias, so the parameter was not able to discriminate the risk of ventricular rhythm disturbances .NLR was significantly increased in patients with UA that developed ventricular arrhythmias  and PT . Cut off values were 11.92% for RDW  and 13.3 s for PT . RDW remained independent predictor of ventricular rhythm disturbances in STEMI patients after multivariate analysis .The following parameters were found to have an acceptable ability in predicting ventricular arrhythmias in STEMI patients: RDW , 0.647 for NEU, 95% CI 0.595–0.697, (p = 0.001) and respectively 0.657 for HGB, 95% CI 0.607–0.704, (p = 0.0003). Cut off values were 13.48 × 10³/μL for leucocyte , 7.744 × 10³/μL for NEU , 12.9 g/dL for HGB (sensitivity 51% and specificity 75.9%).WBC, NEU, and HGB can discriminate STEMI patients with ventricular arrhythmias risk but with a lower accuracy. AUC was 0.634 for leukocyte, 95% CI 0.581–0.684, (p < 0.001) and respectively 0.772, 95% CI 0.728–0.811, (p < 0.001). The cut off values were 14.6 × 10³/μL for WBC  and 7.763 × 10 ³/μL for NEU . NLR was a poor predictor of ventricular rhythm disturbances , with a cut of value of 3.93 .A number of 24 patients with interventional revascularization therapy from the ACS group that developed ventricular arrhythmias had significantly increased WBC, NEU, and NLR . WBC andp < 0.001, and respectively 5.27 ± 6.23 vs. 3.74 ± 4.40, p = 0.013) but these parameters failed as predictors of atrial fibrillation in the studied group .LR and NLR were significantly higher in the group of patients with ACS that developed atrial fibrillation  but it was not a reliable predictor for atrial fibrillation . PLR was also higher in patients with STEMI who developed atrial fibrillation  with AUC 0.660, 95% CI 0.608–0.709, (p = 0.06) and no accuracy for prediction of atrial fibrillation.There were 18 patients with STEMI that developed atrial fibrillation. NLR was significantly increased in these patients  NLR was significantly increased 5.92 ± 7.87 vs. 3.68 ± 3.65, (p = 0.01) and also PLR was increased 197.74 168.04 vs. 121.10 69.26 (p < 0.001). NLR had an AUC 0.502, 95% 0.456–0.547 (p = 0.96) and PLR had an AUC 0.615, 95% CI 0.566–0.663, (p = 0.18) and were not able to discriminate atrial fibrillation risk in this group of patients.In ACS patients treated with PCI who developed atrial fibrillation (p = 0.006), NEU (p < 0.001), WBC (p < 0.001), PLR (p < 0.001), and NLR (p < 0.001) were significantly higher in ACS patients who developed heart failure , NEU , and HGB  have discriminative power for heart failure detection. A cut off value of 13.92 × 10³/μL for WBC has sensitivity of 43.9% and a specificity of 82.4%, and a value over 6.845 × 10³/μL for NEU has a sensitivity of 65.7% and a specificity of 56.7% for predicting heart failure development. In a multivariate regression analysis WBC  remained independent predictor of heart failure. Other independent predictors were age  and creatinine . A cut off value of 13.6 g/dL for HGB has a sensitivity of 62.93% and a specificity of 59.02% for heart failure prediction.WBC  but failed to discriminate for heart failure development .A number of 16 patients with UA developed heart failure and PDW was significantly increased in this group, 21.13 ± 1.82% vs. 20.07 ± 1.30%, (n = 22), WBC (p = 0.005), NEU (p = 0.001), PLR (p = 0.034), and also RDW (p = 0.026) were significantly higher (In NSTEMI patients who developed heart failure (y higher .p < 0.0001) and a value over 14.04% can identify patients at risk of heart failure with a sensitivity of 68.7% and a specificity of 93.7%. RDW persisted as an independent predictor for heart failure after multiple regression analysis . NEU and WBC also had an acceptable ability to predict heart failure . NEU of more than 6.13×10 ³/μL had a sensitivity of 87.5% and a specificity of 51.5% for heart failure occurrence; WBC of more than 11.86 × 10 ³/μL are predicting heart failure with a sensitivity of 68.75% and a specificity of 69.7%. PLR  failed to prognosticate heart failure in NSTEMI patients.RDW had a good ability to predict heart failure in NSTEMI patients , NEU (p = 0.001), PLR (p = 0.024), and NLR (p = 0.027) were found in these patients (p = 0.19), NEU , PLR , and NLR  did not have enough accuracy for detecting heart failure.A number of 78 patients with STEMI developed heart failure and increased WBC (patients . Howevern = 42), PT (p = 0.04), NLR (p = 0.02), PLR (p = 0.03), and RDW (p < 0.001) were significantly increased (p = 0.0001) with a cut off value of 12.53% . The rest of parameters PT , NLR , and PLR  failed to predict heart failure in patients treated with interventional revascularization therapy.In ACS patients treated with PCI who developed heart failure (ncreased . The onlp = 0.045). The AUC was 0.790, 95% CI 0.740–0.834, p = 0.016) that denotes an acceptable ability to predict future short term ischemic events with a cut off value of 1.398 .Only four patients with UA developed during hospitalization a MI. A lower lymphocyte number was found in these patients  and has an excellent predictive value for short term ischemic events . A cut off value of 4.04 has a sensitivity of 75% and a specificity of 87.7%. PLR was higher in patients complicated with MI  and has an acceptable ability to predict ischemic events on short term . A cut off value of 178.224 has a sensitivity of 50% and a specificity of 90.5%.NLR was increased in UA patients that developed in-hospital MI , PT (p < 0.001), NLR (p = 0.001), and PLR (p = 0.03) were significantly higher, and lymphocytes (p = 0.03) were significantly lower . PLR had a good discriminative ability  with a cut off of 197.088 . NLR  failed to predict myocardial ischemia on short term.In ACS patients treated with PCI that experienced recurrent myocardial ischemic event . Lymphocyte had a very poor discriminative value with an AUC of 0.570, 95% CI 0.521–0.618, (p = 0.012). A value of ≤1.982 × 10³/μL had 55.96% sensitivity and 58.04% specificity to identify a more extensive coronary artery disease.Lymphocyte number were significantly lower in patients with three vessel disease (2.10 ± 1.01 × 10³/μL) compared with one vessel (2.35 ± 1.14 × 10³/μL) . In addition, there is a possibility that all of the aforementioned mechanisms may be involved in both erythroid cells poiesis and bone marrow response .WBC are involved in the destabilization of atherosclerosis plaque of ACS patients. In the present study, admission WBC and NEU count were correlated with in-hospital mortality in ACS, especially in NSTEMI patients. Other studies found similar results: elevated WBC was a relevant risk factor for death during the first 30 days to 6 months in patients with UA and NSTEMI in the study of Sabatine et al.  and elevLeukocyte and NEU had an acceptable predictive power for adverse outcome in patients with ACS, especially NSTEMI patients. In patients with STEMI or in patients treated with PCI the discriminative power was lower. However, in another study performed by Chia et al. in patients with STEMI elevated WBC and neutrophils are found to be predictors of adverse cardiac events . In patiWBC and NEU were found to have an acceptable discriminative power for predicting ventricular rhythm disturbances in ACS patients and in patients treated with PCI. Rahimi et al. in a multicenter study revealed that the only predictor for malignant ventricular arrhythmia in NSTEMI patients treated with early invasive strategy was WBC . A correThere are some suggested mechanisms considered as being the potential basis for correlating high levels of WBC with complications and/or death. Development of resistance to thrombolytic therapy is the natural result of changes  in the microcirculation. Between all these factors, after an acute MI, leucocytes have a main function in the initial inflammatory response with a repairing role, which favors the formation of a scar (instead of necrotic tissue). According to experimental data that suggest the existence of a linear association between the size of necrotic tissue and the levels of leukocyte and systemic response, it can be deduced that the larger the size of the infarction, the greater the leukocyte response. It is obvious that infarcts of larger sizes more frequently predispose to the development of complications ; therefore, the fact that the size of the infarction is reflected in the number of red blood cells has a potential prognostic relevance .NLR is the combination of two independent markers of inflammation and was found to be a predictor of short and long-term mortality in patients with ACS . In seveIn a retrospective study performed by Ayca et al. a high NLR was associated with stent thrombosis in patients with STEMI . A NLR >LYM cause a modulation of the inflammatory response and a low LYM count is associated with more extensive atherosclerosis  and withA lower value of HGB is a predictor of in-hospital mortality and complications in ACS patients in our study. Also, a lower HGB is correlated with adverse outcome in STEMI patients and was found to be a predictor of ventricular rhythm disturbances and heart failure in ACS patients. Furthermore, a low HGB level at admission was correlated with recurrent myocardial ischemic events in PCI patients. In the INTERACT trial low HGB at admission was associated with recurrent ischemia ,41. AnemPLR is a parameter which is describing the systemic inflammatory response and was correlated with in-hospital mortality in patients with UA from our study, but the number of these patients was low. Other studies also observed that PLR correlates with greater overall mortality in patients with NSTEMI  and STEMPDW indicates varied size of platelets. The presence of large sized immature platelets in patients with ACS is due to increased bone marrow activity. PDW was found to be a good predictor for long term mortality after AMI ,51. In oMPV is an indicator of platelet size and an activation marker and is correlated in several studies with adverse cardiac outcomes in patients with ACS. MPV is a predictor of impaired reperfusion and six-month mortality in patients with STEMI  and NSTEThe mechanisms involved in understanding MPV are not yet fully known. In the case of patients with ACS, several theories explain the increased platelet volume, one of them stating that after consuming the normal platelets in size, several large, immature platelets are released into the bloodstream . AnotherAlso, for patients who have suffered acute coronary events, the pathophysiology that underlies the increased levels of hematological markers mentioned and discussed above is still not clearly established. Literature data suggested specific mechanisms regarding certain parameters ; however, none of them enjoyed a global agreement in thei regard. Certainly, in order to optimize the treatment and management in patients with established coronary heart disease, additional research is needed to facilitate the understanding and explanation of the basic mechanism by which coagulation profile, hematological indices, ACS incidence and, as well, apparition and development of complications are associated ,64.In the present study the coagulation parameter PT was able to predict mortality and complications in ACS patients, including in the subgroup of patients interventional managed. PT had the best discriminative power for mortality with a value over 14.95 s having a sensitivity of 64.8% and a specificity of 80.1% in detecting patients with risk of death, especially in the subgroup of patients with STEMI. In another study in patients with ACS undergoing PCI, a prolonged PT measured at admission was associated with all-cause mortality and may be used to identify high risk patients . In patiHematological parameters derived from hemogram obtained with modern automated equipment, wide and easily available in clinical practice, and also at an affordable price could become important tools for in-hospital clinical surveillance and for risk stratification of patients with ACS. These parameters add independent information to other clinical and paraclinical variables in short term risk stratification. According to recent studies, it seems that their prognostic value is increasing if they are used in combined analysis with other biomarkers or with risk scores like GRACE or SYNTAX score.Both coagulation and hematological parameters are considered as having a good potential in being used as diagnostic and/or prognostic markers; they are also wide and easily available and can be correlated with short term in hospital outcome in patients with ACS. WBC, RDW, and PT were found to be predictors of poor outcome and can contribute to risk stratification of ACS patients and identification of those subjects that will need close monitoring and intensified treatment. The fastest and most efficient classification of those who are at higher risk is a valuable tool that facilitates their monitoring and careful management by the cardiologist; it also allows judicious and optimal programming in order to follow the patient’s evolution, thereby implicitly leading to the reduction of mortality.


Very early onset inflammatory bowel disease (VEOIBD) patients are known to have special disease characteristics. Limited data is available regarding biologic use and long-term outcomes in VEOIBD patients.We aimed to assess long-term outcomes and time to progression to biologic treatment in VEOIBD patients. Secondary aim was to determine Infliximab prescribing practice during the course of treatment.We retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics, symptoms at diagnosis, disease location and severity were documented. Data on biologic treatment at initiation and during follow up including type of biologic, dosing and response were collected. Kaplan Meier curves were used to assess the number of years to progression to biologic treatment and the parameters influencing commencement. Infliximab dosing and intervals were recorded for all patients treated with Infliximab during induction, after one year and at last follow up.89 patients with VEOIBD were diagnosed during the study period. Median age at diagnosis was 3.8 years (IQR 2.6–5.1), 45.3% had Crohn’s disease (CD) and 62.8% were males. Median duration of follow up was 6.39 years (IQR 3.71–10.55). Biologic treatment was started on 39.5% of patients and 7.1% underwent surgery. In patients with CD, the addition of perianal fistulizing disease or stricturing disease was associated with more rapid progression to biologic treatment . In patients with UC, disease severity (p=0.017) was associated with early initiation of a biologic. The median Infliximab dose at one year was 10 mg/kg (IQR 7.5–11) with median dose interval of 4 weeks (IQR 4–6). At the time of the last follow up, 18 patients (72%) maintained treated with Infliximab and had a median dose of 9 mg/kg per dose (IQR 8.1–10) and a median dose interval of 4.5 weeks (IQR 4–6). Clinical remission was reported in 61.8% of patients on their first biologic agent at the last follow up.Factors influencing earlier progression to biologics were disease severity and disease behaviour. The response rate was higher than previously reported and might be due to higher Infliximab dosing with shorter infusion intervals than standard dosing.None


This paper characterizes the personal PM2.5 exposure and protocol compliance measured with a wearable sensor. The MicroPEM™ collected personal continuous and integrated measures of PM2.5 exposure and compliance data on 272 children. PM2.5, black carbon (BC), and brown carbon tobacco smoke (BrC-ETS) exposure was measured from the filters. We performed a multivariate analysis of woodstove presence and other factors that influenced PM2.5, BC, and BrC exposures. We collected valid exposure data from 258 of the 272 participants (95%). Children wore the MicroPEM for an average of 46% of the 72-h period, and over 80% for a 2-day, 1-night period (with sleep hours counted as non-compliance for this study). Elevated PM2.5 exposures occurred in the morning, evening, and overnight. Median PM2.5, BC, and BrC-ETS concentrations were 8.1 μg/m3, 3.6 μg/m3, and 2.4 μg/m3. The combined BC and BrC-ETS mass comprised 72% of the PM2.5. Woodstove presence, hours used per day, and the primary heating source were associated with the children’s PM2.5 exposure and air filters were associated with reduced PM2.5 concentrations. Our findings suggest that woodstove smoke contributed significantly to this cohort’s PM2.5 exposure. The high sample validity and compliance rate demonstrated that the MicroPEM can be worn by young children in epidemiologic studies to measure their PM2.5 exposure, inform interventions to reduce the exposures, and improve children’s health.As part of the New Hampshire Birth Cohort Study, children 3 to 5 years of age participated in a personal PM Seminal epidemiological studies demonstrated children’s exposure to particulate matter (PM) adversely impacts pulmonary development leading to a long-term trajectory of chronic respiratory diseases such as asthma ,2,3, broTo measure or estimate a child’s PM exposure, previous studies relied upon surrogate measures. Frequently employed PM exposure assessment approaches include the nearest government-operated ambient monitor, deployment of study specific stationary indoor or outdoor monitors, and land use regression models. One reason for surrogate measurements is that the burden of personal exposure monitoring on the children or parents historically has been very high. Children, especially young children , cannot physically wear traditional personal monitoring equipment consisting of a separate pump and sampler that could weigh up to 2 kg. Previous attempts to collect pseudo personal level exposure measurements on young children by the parents keeping a lunchbox-sized package near the child collected valid samples, but the representativeness of the data was questionable because parent surveys reported low compliance because of the burden . The dev2.5 personal exposure data from children aged between 3 and 5 years of age. Our objectives were to assess the quality of exposure data collected, identify trends in the integrated and continuous PM2.5 and chemical species exposure concentration data, and examine child, parent, and residential characteristics that influence their exposure, including use of a woodstove.As part of the New Hampshire Birth Cohort Study (NHBCS), we report the use of wearable, low burden instrumentation to collect PM2.5 exposures from March 2017 to February 2020. Participant demographic information, and home heating and tobacco smoke survey data were collected using the NHBCS Early Childhood Environment Checklist and since July 2019 the ECHO Household Exposure to Secondhand Smoke—Childhood questionnaire (The New Hampshire Birth Cohort Study (NHBCS) is an ongoing, prospective study of rural pregnant women and their children, and is a pediatric cohort for the NIH-funded Environmental influences on Child Health Outcomes (ECHO) program. The primary aim of the NHBCS is to investigate the effects of environmental exposures, including use of wood stoves, on fetal growth and childhood development. A subset of 272 children 3 to 5 years of age participated in a personal monitoring study of PMionnaire . The stu2.5 exposure was measured with the RTI MicroPEM™  placed inside an animal-themed front facing halter vest . Embedded temperature and relative humidity sensors automatically corrected the nephelometer concentration [Children’s PMter vest . Study pntration . A 3-axintration . A rolliThe integrated filter enables gravimetric and chemical analyses that identify exposures to multiple PM species. Gravimetric analysis consisted of triplicate weights pre- and post-sample collection conducted on a Mettler UTM2 digital balance  inside a constant temperature (21 °C) and relative humidity (35%) chamber . The met2.5 mass concentrations were processed to clean the data. The 10-s nephelometer data were corrected for the nephelometer offset that prevented measurement of negative concentrations and adjusted for baseline shift if necessary [2.5. We considered minimum thresholds from 60% to 30%, and selected 30% based on the distribution of compliance values measured in this study and the threshold established for similar analyses performed for other cohorts [MicroPEM nephelometer data files with valid PMecessary . Adjuste cohorts ,13,172.5, BC, and BrC-ETS exposure. We restricted models for PM2.5 and BrC to the non-smoking households to control for potential confounding , average number of hours per day of use of a woodstove, whether a woodstove was their primary heating source, and whether they had a household air filter. In addition, sensitivity analyses were run by limiting study population to the households without air filters. We adjusted for factors related to the measurements of interest in either univariate models or fully adjusted models. For models of PM2.5 levels, we included BMI at 3 years of age, average number of hours of sleep per night, and season  as covariates. For BrC levels, we included the child’s age and BMI at 3 years of age, and for BC levels, we included the mother’s enrollment age, and maternal and paternal level of education in the models. Each season: fall, winter, spring (excluding summer as a reference level), as well as the exposures: wood stove (yes /no), woodstove primary heating source (yes/no), a single air filter in use (yes/no), were modeled as binary variables. Ordinal variables such as maternal and paternal education were treated as continuous variables as well as child’s BMI, age, maternal age at enrollment, hours of sleep per night, and exposure variable hours of woodstove use per day on average.A multivariate analysis of the data subset with wearing compliance greater than 30% was performed to identify parent, child, and household factors that influence PMfounding , whereasOf the 272 participants, 258 (95%) provided a valid MicroPEM sample for exposure characterization. Invalid samples resulted from battery failure prior to 22 h of data collection (n = 10), the child removed the inlet cap (n = 2), child turned off the MicroPEM (n = 1), and withdrawal from the exposure study (n = 1). The mean sample duration was 74.6 ± 17.3 hrs, with a maximum of 138 hrs. The wearing compliance of the 258 children with a valid sample  was norm2.5 mass concentration was 8.0 μg/m3 (GSD = 1.9). The median BrC-ETS concentration was higher than BC (3.5 μg/m3 versus 2.3 μg/m3) but the GSDs were equal at 2.0  and one filter was punctured during post-collection analysis. The median PMl at 2.0 . The fraectively . PM2.5 m3 during data collection. Mean 1-min average PM2.5 concentration was 6.5 μg/m3 with a range from 1.6 to 116.6 μg/m3 . Hourly PM2.5 concentration median and quartiles across the 240 valid nephelometer files follow similar temporal pattern. Although the temporal variability in the median and 1st quartile spans a smaller range, spanning < 4.8 μg/m3 versus 8.7 μg/m3 for the mean and 3rd quartile, any of the descriptive statistic measures can illustrate temporal trends.The distribution of PMs cohort . The PM22.5, BrC, and BC concentrations and woodstove smoke exposure, expressed as woodstove use (yes/no) and the average number of hours of woodstove use per day  increase in personal PM2.5 levels. Use of an air filter decreased PM2.5 levels 23.3% . Use of a woodstove was associated with 22.3%  increase in personal BrC levels and each additional hour of woodstove exposure was associated with 1.0%  increase in BrC exposure. Similarly, having a woodstove was associated with an 18.9%  increase in BC personal levels and each additional level of woodstove exposure was associated with a 1.6%  increase in BC exposure. Woodstove use as the primary heating source as a dichotomized variable was not clearly associated with PM2.5 or BrC levels, but was related to a 13.3%  increase in BC.We observed statistically significant association between personal PM per day . Results per day . Using aIn a rural cohort from northern New England, young children wore the MicroPEM as instructed. Although the mean compliance of 46% seems low, this value does not credit the child for compliance while asleep with the MicroPEM nearby, as is our typical practice . Parents2.5, BC, and BrC-ETS concentrations and corresponding ratios suggest that combustion sources are likely the primary components of the children’s PM2.5 exposure. BrC-ETS and BC comprise between 39 and 44% and between 28 and 33% of the PM2.5 mass, respectively, for the middle two-thirds of the measurements. The cumulative BC and BrC-ETS contribution to the PM2.5 mass is of 67% to 77% across all samples. This high percentage suggests significant contributions from woodstoves, cigarettes, cooking aerosol, or traffic related air pollution. For the lowest 5% of PM2.5 concentrations, BrC-ETS is not present, but the presence of BC is suggestive of diesel engine or candle emissions. Black carbon and ultrafine particle exposure are associated with adverse respiratory health outcomes in children [2.5 concentrations, the BrC-ETS fraction decreases but the BC fraction remains constant potentially indicative of exposure to high concentrations of PM2.5 from multiple sources. Although personal and indoor stationary measures are not a direct comparison, our values agree with a previous study of indoor PM2.5 concentrations in Northern New England residences with woodstoves, but are lower than other reported indoor PM2.5 concentrations in homes with woodstoves that ranged from 17.5 to 32.4 μg/m3 measured in homes with woodstoves [3 and 2.80 μg/m3, respectively) possibly because of the personal versus indoor stationary measures, and parents that smoked cigarettes were enrolled in our study, even though we restricted the multivariate analysis to non-smoking households [The PMchildren ,19,20. Aodstoves ,22,23. Ouseholds .2.5 concentration followed a logical pattern also observed in other studies [2.5 concentrations are at a minimum before increasing to a peak of 13.9 μg/m3 as the children and their families conduct their morning activities. A decrease in children’s PM2.5 exposure to a mean range from 9.2 to 10.2 μg/m3 starting around lunch through late afternoon suggests a quiet time or a cleaner microenvironment possibly outside the home. PM2.5 concentrations increase again in the early evening, likely caused by typical evening activities, before becoming stable through 11 PM. PM2.5 concentrations, then slowly decay while the family is asleep.Temporal trends in the mean hourly PM studies ,25,26. S2.5 concentrations occur overnight or in the evening in residences with woodstoves. This strongly suggests these young children that reside in a residence with a woodstove receive their peak exposures overnight from woodsmoke or from cooking. Another woodstove smoke exposure study found hourly mean PM2.5 concentrations were most strongly associated with residential activities, where the dominant sources were frying food (34.5 μg/m3), wood stove use (26.4 μg/m3), fireplace use (25.4 μg/m3), and candle burning (20.3 μg/m3) [The maximum hourly average PM3 μg/m3) .2.5 exposure and the presence of one or more air filters may help mitigate PM2.5 exposure. Use of woodstove and hours of use were more clearly associated with PM2.5 exposure than use of woodstove as a primary heating source. This may be because woodstove use and duration of use irrespective of whether it is the primary heating source is more predictive or because of imprecision of our estimates for primary heating. Other studies of indoor air quality inside homes that use wood stoves for residential heating also found woodsmoke was an important source of household PM2.5. Fleisch et al. (2020) found significantly higher organic carbon and potassium, and elevated, but not statistically significant, differences in PM2.5 and BC concentrations in the 29% of homes that used a woodstove compared with those that did not [2.5 concentrations were higher (p = 0.04) for the 14 homes with wood stove use (15.6 μg/m3) than for the 22 homes without (12.6 μg/m3) [2.5 concentrations from woodstoves by 68% [Our analysis supports the hypothesis that woodstove use was a determinant of the children’s PM did not . A Norwe6 μg/m3) . An indos by 68% ,28,29.2.5 exposure assessment on children during early childhood . The exposure assessment techniques used enabled the collection of valid and representative PM2.5 exposure data that can be linked to a specific air pollution source. In this case, young children with a woodstove in their non-smoking home have higher PM2.5 exposures than children who rely on other sources of heat. A limitation of our study was the inability to adjust for other known factors that influence PM2.5 exposure concentration, such as ambient air pollution or environmental inequality, to assess their impact on young children’s exposure. The success of this PM2.5 exposure characterization analysis enables future research with other cohorts to associate the direct measurement of a young child’s PM2.5 exposure during this susceptible period of their pulmonary development. Our findings suggest that personal monitoring children’s PM2.5 exposures from woodstove exposure is a feasible approach for future epidemiologic studies designed to inform interventions to reduce the exposures and improve children’s health.This study is among the first to conduct a personal PM