Nationwide Multicenter Study Research Articles

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

Aims/hypothesisCoronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.MethodsWe conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.ResultsThe current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.Conclusions/interpretationsIn people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.Trial registrationclinicaltrials.gov NCT04324736.

Clinical characteristics and prognosis in a large paediatric cohort with status epilepticus

PurposeTo describe the aetiology, clinical features, and short-term outcomes of children with status epilepticus (SE), in particular super-refractory SE (SRSE), by a nationwide multicentre study in China. MethodsIn this retrospective study, inpatient children with SE were identified from neurology departments and paediatric intensive care units from 44 hospitals in 27 provinces of China between 2013 and 2015. Clinical data were exported from the Hospital Information System. ResultsClinical records from children with SE (n = 4255) aged 1 month to 18 years were enrolled; 13.1 % were diagnosed with SRSE. The most common known SE aetiology was acute symptomatic aetiology (42.8 %) and 50.2 % of SE was caused by epilepsy of unknown aetiology. Acute central nervous system (CNS) infections (38.8 %) were associated with SRSE (P < 0.001). The overall SE in-hospital mortality rate was 3.0 %, which was significantly higher in the children with SRSE than in those with non-SRSE (15.2 % versus 1.4 %, respectively; P < 0.001). Fourteen percent of the children with SE had various levels of neurological dysfunction at discharge. SRSE was a risk factor for in-hospital mortality (hazard ratio = 4.14; 95 % confidence interval [CI]: 2.34−7.32; P < 0.001) and neurological dysfunction at discharge (odds ratio = 2.85; 95 % CI: 1.90−4.27; P < 0.001). ConclusionAcute symptomatic aetiology was the most common known cause of paediatric SE. Aetiology was associated with progression to SRSE and short-term neurological dysfunction at discharge. Furthermore, SRSE was considered a risk factor for in-hospital mortality and short-term neurological dysfunction.

Prevalence, Epidemiology, Etiology, and Sensitivity of Invasive Bacterial Infections in Pediatric Patients Undergoing Oncological Treatment: A Multicenter Nationwide Study.

Background: Infectious complications (IC) caused by bacterial strains often impede anticancer therapy. The study aimed to retrospectively analyze bacterial IC that could help predict the risk and optimize the empirical treatment for bacterial infections in pediatric cancer patients. Patients and Methods: Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM including acute leukemias, Hodgkin and non-Hodgkin lymphomas [NHLs], and Langerhans cell histiocytosis) and 3,158 with solid tumors (STs including central nervous system tumors, neuroblastoma, Wilms' tumor, soft tissue sarcoma, germ cell tumors, Ewing sarcoma, osteosarcoma, hepatoblastoma, and others) were enrolled into the study. Episodes of bacterial infectious complications (EBICs) confirmed by microbiological findings were reported by each hospital and analyzed centrally. Results: At least 1 EBIC was diagnosed in 2,155 (36.8%) children (1,281 [59.4%] with HM and 874 [40.6%] with ST; p < 0.001). All-in 4,860 EBICs were diagnosed including 62.2% episodes in children with HM and 37.8% in children with ST (p < 0.001). Having analyzed the source of infections, blood stream infections predominated, apart from NHL patients in whom the most common type was gut infections. The profile of bacteria strains was different in HM and ST groups (p < 0.001). However, in both groups the most common Gram-negative pathogen was Enterobacteriaceae, with the rate being higher in the HM group. Among Gram-negative strains low susceptibility to ceftazidime, whereas among Enterococcus spp. low susceptibility to vancomycin was noticed. The rate of multidrug-resistant (MDR) pathogens was high, especially for Gram negatives (47.7% vs. 23.9%; p < 0.001). The survival after infections was comparable for HM and ST patients (p = 0.215). Conclusions: The risk of bacterial IC in HM patients was higher than in the ST group. The high rate of MDR strains was detected in pediatric cancer patients, especially in those with HM.

Efficacy of rituximab in patients with Graves' orbitopathy: a retrospective multicenter nationwide study.

The clinical utility of rituximab (RTX) in Graves' orbitopathy (GO) treatment remains controversial since the discrepant results from 2 prospective randomized studies (Stan M et al. J Clin Endocrinol Metab 2015; Salvi M et al. J Clin Endocrinol Metab 2015). The aim of this study was to assess in real life the characteristics and the clinical outcomes of patients with GO treated with RTX in cases of corticosteroid resistance or corticosteroid dependence. Multicenter French retrospective study including patients with moderate-to-severe GO requiring second-line treatment with RTX. Patients were classified according to three main baseline characteristics: clinical inflammation (CAS ≥ 3), oculomotor limitation, and visual dysfunction. Patients were considered as responders if, at 24weeks (week 24), at least 1 of these 3 parameters improved with no worsening elsewhere. Forty patients were included (65% smokers, 38% dysthyroidism). Thirty-two patients were treated with RTX alone (one patient excluded owing to side effects): 64.5% had favorable responses at week 24 and significant reduction in baseline CAS (3.29 ± 1.6) at 12weeks (1.93 ± 1.1; P < 0.001) and at week 24 (1.59 ± 1.1; P < 0.001); reduction in anti-TSH receptor antibodies at week 24 (P < 0.01); and significant improvement of visual acuity (P = 0.04) and ocular hypertonia (P = 0.04) at week 12, but no improvement in oculomotor dysfunction. Eight patients needed emergency treatment with concomitant RTX and orbital decompression, with favorable outcome for 5 patients. Predictive factors for a poor response to RTX were low baseline CAS, smoker, and baseline ocular hypertonia. All patients reported good tolerance except one serious side effect (a cytokine release syndrome). The efficiency results of RTX in reducing CAS in this cohort are just between those of Stan and Salvi. This could be explained by our delay before treatment initiation, quicker than Stan but longer than Salvi. RTX appears to be effective as a second-line treatment for the inflammatory component of GO, especially if the disease is highly active and recent.

Genomic ancestry and glycemic control in adolescents with type 1 diabetes: A multicenter study in Brazil.

To determine the influence of genomic ancestry (GA) and self-reportedcolor-race (SRCR) on glycemic control in adolescents with type 1 diabetes (T1D) in an admixed population. This multicenter nationwide study was conducted in 14 public clinics in 10 Brazilian cities. We estimated global and individual African, European, and Native Amerindian GA proportions using a panel of 46 AIM-INDEL markers. From 1760 patients, 367 were adolescents (20.9%): 184 female (50.1%), aged 16.4 ± 1.9 years, age at diagnosis 8.9 ± 4.3 years, duration of diabetes 8.1 ± 4.3 years, years of study 10.9 ± 2.5 and HbA1c of 9.6 ± 2.4%. Patients SRCR as White: 176 (48.0%), Brown: 159 (43.3%), Black: 19(5.2%), Asians: 5 (1.4%) and Amerindians: 8 (2.2%). The percentage of European GA prevailed in all groups: White (71.1), Brown (58.8), Black (49.6), Amerindians (46.1), and Asians (60.5). Univariate correlation was noted between A1c and African GA, r = 0.11, P = .03; years of study, r = -0.12 P = .010, and having both private and public health care insurance (r = -0.20, P < .001). After adjustments, the multivariate logistic analysis showed that SRCR or GA did not influence glycemic control. A high percentage of European GA was noted in our patients, even in those who self-reported as non-White, confirming the highly admixed ethnicity of the Brazilian population. Better glycemic control was associated with having both types of health care; however, there was no association between glycemic control with GA or SRCR. Future prospective studies with other admixed populations are necessary to confirm our findings.

Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

Pakistan is fifth among high burden countries for tuberculosis. A steady increase is seen in extrapulmonary tuberculosis (EPTB), which now accounts for 20% of all notified TB cases. There is very limited information on the epidemiology of EPTB. This study was performed with the aim to describe the demographic characteristics, clinical manifestations and treatment outcomes of EPTB patients in Pakistan. We performed descriptive analysis on routinely collected data for cohorts of TB patients registered nationwide in 2016 at health facilities selected using stratified convenient sampling. Altogether 54092 TB including 15790 (29.2%) EPTB cases were registered in 2016 at 50 study sites. The median age was 24 years for EPTB and 30 years for PTB patients. The crude prevalence of EPTB in females was 30.5% (95%CI; 29.9-31.0) compared to 27.9% (95%CI; 27.3-28.4) in males. The likelihood of having EPTB (OR), was 1.1 times greater for females, 2.0 times for children, and 3.3 times for residents of provinces in the North-West. The most common forms of EPTB were pleural (29.6%), lymphatic (22.7%) and abdominal TB (21.0%). Pleural TB was the most common clinical manifestation in adults (34.2%) and abdominal TB in children (38.4%). An increase in the prevalence of pleural and osteoarticular and decline in lymphatic and abdominal TB was observed with advancing age. Diversity in demography and clinical manifestations were noted between provinces. The treatment success rate for all type EPTB was significantly high compared to bacteriology confirmed PTB with the exception of EPTB affecting CNS with a high mortality rate. The study provides an insight into demography, clinical manifestations and treatment outcomes of EPTB. Further studies are needed to explain significant diversities observed between provinces, specific risk factors and challenges concerning EPTB management.

Risk of hospitalisation associated with benzodiazepines and z-drugs in Italy: a nationwide multicentre study in emergency departments.

Benzodiazepines (BZD) and z-drugs (ZD) are a widely prescribed group of medicines. They are often used inappropriately, and this is associated with adverse events (AEs), which may cause emergency department (ED) visits. The present study aimed to describe the characteristics of BZD and ZD related AEs leading to emergency department (ED) visit and hospitalisation in Italy, considering their plasma half-life. Ninety-two Italian EDs were monitored between 2007 and 2018. Rates of ED visit and hospitalisation were calculated. Multivariate logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation. Univariate linear regression was performed to evaluate the ROR of hospitalisation according the plasma half-life of the suspected agents. A total of 3203 AE reports were collected. Overall, multivariate logistic regression showed that the risk of hospitalisation was higher for prazepam (3.26 [1.31-8.11]), flurazepam (1.62 [1.15-2.27]), and lorazepam (1.36 [1.15-1.61]). In the elderly, this risk was higher for prazepam (3.98 [1.03-15.3]), and lorazepam (1.58 [1.19-2.11]). Parenteral and rectal formulations were associated with a lower risk of hospitalisation compared to oral formulations. Our findings underlined the dangers in the use of BZD and ZD in Italy, particularly in women and older adults. ED clinicians must always take into account that the higher risk in terms of hospitalisation related to the use of BZD and ZD can be observed in patients treated with oral formulations, in those exposed to more than one sedative-hypnotics, and in patients exposed to compounds with intermediate or long plasma half-life.

Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P=.151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Molecular epidemiology and resistance patterns of blaOXA-48Klebsiella pneumoniae and Escherichia coli: A nationwide multicenter study in Taiwan.

We describe the molecular epidemiology and resistance patterns of blaOXA-48Klebsiella pneumoniae and Escherichia coli in Taiwan. In this multicenter surveillance study from January 2012 to August 2015, the identified blaOXA-48Enterobacteriaceae isolates were subjected to antibiotics susceptibility testing. PCR method was used for detecting concomitant other beta-lactamases. Outer membrane porins were analyzed. Genetic relatedness and molecular epidemiology of the isolates were determined through pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid incompatibility was determined using PCR-based replicon typing. Forty-three blaOXA-48K. pneumoniae and two E. coli isolates were analyzed. The annual incidence of blaOXA-48K. pneumoniae isolates from 2012 to 2015 were 0%, 1.1%, 2.4%, and 7.6%, respectively. Forty-three (95.5%) of 45 isolates were non-susceptible to broad-spectrum beta-lactams (ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam), Forty-two (93.3%) of the 45 isolates showed resistance against all tested carbapenems (imipenem, meropenem, doripenem, and ertapenem). Molecular characterization revealed that they co-produced at least one extended-spectrum beta-lactamases or AmpC beta-lactamases, with at least one outer membrane porin loss. Thirty-eight (88.3%) of the 43 K. pneumoniae isolates belonged to ST11. PFGE analysis of 43 K. pneumoniae isolates revealed dissemination of multiple clones. Six of the 12 tested K. pneumoniae representatives of different pulso-types belonged to IncA/C. Concomitant loss of porins and production of other beta-lactamases renders the blaOXA-48-producing isolates in Taiwan a high-level carbapenem resistance and broad resistance against many beta-lactam antibiotics. Following dissemination of multiple clones of blaOXA-48K pneumoniae ST 11, a trend of increased blaOXA-48 prevalence was noted.

Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization.

BACKGROUNDTransarterial chemoembolization (TACE) is recommended for patients with intermediate hepatocellular carcinoma (HCC) according to treatment guidelines. However, a large number of patients with advanced HCC also receive TACE in clinical practice, especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score (ECOG) 1. In view of previous studies, such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread; therefore, patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment, but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking.AIMTo investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model.METHODSPatients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016. Overall survival (OS) was estimated using Kaplan–Meier curves and compared by the log-rank test. Multivariate Cox regression was used to develop the potential prognostic models. The discriminatory ability of the models was compared and validated in various patient subgroups. The individual survival prediction for six-and-twelve (6&12) criteria, defined as the algebraic sum of tumor size (cm) and tumor number, was illustrated by contour plot of 3-year survival probability and nomogram.RESULTSA total of 792 eligible patients were included. During follow-up, median OS reached 18.9 mo [95% confidence interval (CI): 16.9-21.0]. Three independent multivariate analyses demonstrated that tumor size, tumor number, α-fetoprotein level, albumin–bilirubin grade and total bilirubin were prognostic factors of OS (P < 0.05). The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability. In addition, the 6&12 criteria was correlated with OS in various subgroups of patients. The patients were stratified into three strata with score ≤ 6, > 6 but ≤ 12, and > 12 with different median OS of 39.8 mo (95%CI: 23.9-55.7), 21.1 mo (95%CI: 18.4-23.8) and 9.8 mo (95%CI: 8.3-11.3), respectively (P < 0.001).CONCLUSIONTACE is effective for advanced HCC patients with ECOG 1 alone, and the 6&12 criteria may help with clinical decision-making.

HLA class II genotyping of admixed Brazilian patients with type 1 diabetes according to self-reported color/race in a nationwide study

The HLA region is responsible for almost 50% of the genetic risk of type 1 diabetes (T1D). However, haplotypes and their effects on risk or protection vary among different ethnic groups, mainly in an admixed population. We aimed to evaluate the HLA class II genetic profile of Brazilian individuals with T1D and its relationship with self-reported color/race. This was a nationwide multicenter study conducted in 10 Brazilian cities. We included 1,019 T1D individuals and 5,116 controls matched for the region of birth and self-reported color/race. Control participants belonged to the bone marrow transplant donor registry of Brazil (REDOME). HLA-class II alleles (DRB1, DQA1, and DQB1) were genotyped using the SSO and NGS methods. The most frequent risk and protection haplotypes were HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 (OR 5.8, p < 0.00001) and HLA~DRB1*07:01~DQA1*02:01~DQB1*02:02 (OR 0.54, p < 0.0001), respectively, regardless of self-reported color/race. Haplotypes HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 and HLA~DRB1*04:02~DQA1*03:01 g~DQB1*03:02 were more prevalent in the self-reported White group than in the Black group (p = 0.04 and p = 0.02, respectively). The frequency of haplotype HLA~DRB1*09:01~DQA1*03:01 g~DQB1*02:02 was higher in individuals self-reported as Black than White (p = <0.00001). No difference between the Brazilian geographical regions was found. Individuals with T1D presented differences in frequencies of haplotypes within self-reported color/race, but the more prevalent haplotypes, regardless of self-reported color/race, were the ones described previously in Europeans. We hypothesize that, in the T1D population of Brazil, although highly admixed, the disease risk alleles come mostly from Europeans as a result of centuries of colonization and migration.

Brazilian autoimmune encephalitis network (BrAIN): preliminary results from a nationwide multicentric study (1646)

Brazilian autoimmune encephalitis network (BrAIN): preliminary results from a nationwide multicentric study (1646)

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

BackgroundThe decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AimTo determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. MethodsThis was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. ResultsA total of 1136 patients completed the questionnaire. Patients’ CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. ConclusionsThe average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Survival and complications in hinged knee reconstruction prostheses after distal femoral or proximal tibial tumor resection: A retrospective study of 161 cases

IntroductionHinged knee megaprostheses are mainly used for reconstruction after tumor resection. They may incur complications, but this has not been assessed in the French literature, except in small series at short follow-up. We therefore conducted a large-scale nationwide multicenter retrospective study with a minimum 5 years’ follow-up. The objectives were (1) to compare survival between distal femoral and proximal tibial reconstruction prostheses, and (2) to analyze complications and failure. HypothesisDistal femoral hinged reconstruction prostheses show longer survival with fewer complications than proximal tibial prostheses. Material and methodsOne hundred sixty-one patients were included: 118 in the distal femoral group, and 43 in the proximal tibial group. Tumors were mostly osteosarcomas (90 cases) or chondrosarcomas (31 cases). Mean age was 37 years (range, 12-86 years). Complications were assessed on the Henderson classification. Failure was defined by prosthesis anchor exchange or amputation. ResultsAt a mean 9 years’ follow-up (range, 5-23 years), implant survival was longer in the distal femoral group: 5- and 10-year survival, 84% [95% CI, 75-89] and 70% [95% CI, 59-79] versus 74% [95% CI, 69-85] and 43% [95% CI, 23-61] (p=0.02). Revision surgery for complications mainly concerned aseptic loosening (19%, 30 cases) or deep infection (16%, 25 cases) and more often involved the proximal tibia (65% vs. 43%, 28 vs. 51 cases; OR 2.4 [95% CI, 1.2-5.1]; p=0.02). DiscussionHinged knee reconstruction prosthesis is a solution in tumoral pathology, but with a high risk of complications (loosening and infection) and a higher failure rate in the proximal tibial reconstruction prosthesis. Level of evidenceIV, case series.

Infectious complications after hematopoietic stem cell transplantation for primary immunodeficiency in children: A multicenter nationwide study.

The aim of this nationwide study was to evaluate the characteristics of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in pediatric patients with PID after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In total, 114 HSCT recipients were enrolled into the study. At least one infectious complication (IC) was diagnosed in 60 (52.6%) patients aged 0.1-17.7years, that is, 59.5% with SCID and 49.4% with non-SCID. Among 60 HSCT recipients diagnosed with at least one IC, 188 episodes of infectious complications (EIC) were recorded, that is, 46.8% of BI, 41.5% of VI, and 11.7% of proven/probable IFD. According to PID and HSCT donor type, the incidence of EIC was comparable (P=.679). The localization of infections differed significantly due to PID type (P=.002). After each HSCT donor type, the most common site of infection was GI. Overall, BI caused by Gram-positive strains (59.1%) were prevalent, especially Staphylococcaceae. The multidrug-resistant (MDR) pathogens were diagnosed in 52.3%, especially ESBL+Enterobacteriaceae. The profile of VI was comparable for SCID and non-SCID patients (P=.839). The incidence of IFD was comparable for each PID and HSCT donor type. Survival after infection was 91.5% and was comparable for PID and HSCT donor type. The rate of patients diagnosed with IC among pediatric PID-HSCT recipients did not depend on PID type, but rather on HSCT donor type. The localization of IC depended on PID and HSCT donor type. Within bacterial infections, predominated Gram-positive strains and the MDR pathogens were responsible for more than half of EIC.

Italian Emergency Department Visits and Hospitalizations for Outpatients' Adverse Drug Events: 12-Year Active Pharmacovigilance Surveillance (The MEREAFaPS Study).

BackgroundAdverse drug event (ADEs) are a significant cause of emergency department (ED) visits and consequent hospitalization. Preventing ADEs and their related ED visits in outpatients remains a public health safety challenge. In this context, the aims of the present study were to describe the frequency, seriousness and preventability of outpatients’ ADE-related ED visits and hospitalizations in the Italian general population, and to identify the presence of potential predictors of ADE-related hospitalization.MethodsWe performed a nationwide, multicentre, observational, retrospective study based on reports of suspected ADEs collected between January 1, 2007 and December 31, 2018 in 94 EDs involved in the MEREAFaPS project. Patients’ demographic characteristics, their clinical status, suspected and concomitant drugs, ADE description, and its degree of seriousness, were collected. Causality and preventability were assessed using validated algorithms, and logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization, considering the following covariates: age, sex, ethnicity, number of implicated medications, parenteral administration, presence of interaction, therapeutic error, and/or complementary and alternative medicines (CAM).ResultsWithin 12 years, 61,855 reports of suspected ADE were collected, of which 18,918 (30.6%) resulted in hospitalization (ADE defined as serious). Patients were mostly female (56.6%) and Caucasians (87.7%), with a mean age of 57.5 ± 25.0 years. 58% of patients were treated with more than two drugs, and 47% of ADEs leading to hospitalization were preventable. Anticoagulants, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently implicated agents for ED visits and/or hospitalization, which included clinically significant ADEs, such as haemorrhage for anticoagulants, moderate to severe allergic reactions for antibiotics, and dermatologic reactions and gastrointestinal disturbances for NSAIDs. Older age (1.54 [1.48–1.60]), higher number of concomitantly taken drugs (2.22 [2.14–2.31]), the presence of drug-drug interactions (1.52 [1.28–1.81]), and therapeutic error (1.54 [1.34–1.78]), were significantly associated with an increased risk of hospitalization.ConclusionOur long-term active pharmacovigilance study in ED provided a valid estimation of ADE-related hospitalization in a representative sample of the Italian general population and can suggest further focus on medication safety in outpatients, in order to early recognise and prevent ADEs.

A Multicenter Study of Antifungal Use and Species Distribution and Antifungal usceptibilities of Candida Isolates in South Korea

Background: Candidiasis control should include monitoring the epidemiology and resistance to various antifungal agents. In this study, the researchers investigated the Candida species recovered from clinical specimens at particular geographic areas or hospitals. Objective: The present study is geared toward the evaluation of antifungal drug usage at Korean hospitals in 2016. It is also essential that species distribution and antifungal susceptibilities of Candida isolates should be looked into to provide important data that can help devise therapeutic strategies to control the disease. Methods: Systemic antifungal agent usage over a one-year period was investigated at 10 Korean hospitals. Identification and antifungal susceptibility tests were performed on clinical isolates of the Candida species, which were collected over a three-month period. Results: The total antifungal usage in each hospital ranged from 7.7 to 158.9 defined daily doses (DDDs) per 1,000 patient days. Fluconazole was most commonly used (37.1%), followed by amphotericin B (30.6%), itraconazole (9.7%), echinocandins (8.8%), voriconazole (7.5%), and posaconazole (6.3%), respectively. Among 274 Candida isolates, C. albicans was the most frequently recovered (51.1%), followed by C. glabrata (15.7%), C. tropicalis (15.0%), and C. parapsilosis (13.5%), respectively. Through the application of either species-specific clinical breakpoints or epidemiological cutoff values to Candida isolates, the non-susceptibility rates to fluconazole, voriconazole, amphotericin B, and micafungin were found in 20.7%, 5.6%, 0%, and 0% of isolates, respectively. Conclusion: This nationwide multicenter study showed that total antifungal use varied considerably according to each hospital. Non-susceptibility to fluconazole should be further monitored, considering the drug's frequent use in Korea.

Reply to the Editor: Surgical Treatment of Osteoporotic Vertebral Fracture with Neurological Deficit-A Nationwide Multicenter Study in Japan.

Reply to the Editor: Surgical Treatment of Osteoporotic Vertebral Fracture with Neurological Deficit-A Nationwide Multicenter Study in Japan.

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

PurposeTo evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes.MethodsThe study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population.ResultsAmong the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes.ConclusionCCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated.

Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

ObjectiveDirect comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation...