bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series
Authors:   the IMAGES (Integrated MAnaGEment of Sepsis) Group, Torti Carlo , Mazzitelli Maria , Longhini Federico , Garofalo Eugenio , Bruni Andrea , Giancotti Aida , Barreca Giorgio Settimo , Quirino Angela , Liberto Maria Carla , Serapide Francesca , Matera Giovanni , Trecarichi Enrico Maria , Navalesi Paolo
Published: October 2019

Background

Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited.

Case presentation

We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures.

The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections.

Conclusions

IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.
Comparison between three different equations for the estimation of glomerular filtration rate in predicting mortality after coronary artery bypass
Authors: Gelsomino Sandro , Bonacchi Massimo , Lucà Fabiana , Barili Fabio , Del Pace Stefano , Parise Orlando , Johnson Daniel M. , Gulizia Michele Massimo
Published: October 2019

Background

This study was undertaken to compare the accuracy of chronic kidney disease-epidemiology collaboration (eGFRCKD-EPI) to modification of diet in renal disease (eGFRMDRD) and the Cockcroft-Gault formulas of Creatinine clearance (CCG) equations in predicting post coronary artery bypass grafting (CABG) mortality.

Methods

Data from 4408 patients who underwent isolated CABG over a 11-year period were retrieved from one institutional database. Discriminatory power was assessed using the c-index and comparison between the scores’ performance was performed with DeLong, bootstrap, and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics.

Results

The discriminatory power was higher in eGFRCKD-EPI than eGFRMDRD and CCG (Area under Curve [AUC]:0.77, 0.55 and 0.52, respectively). Furthermore, eGFRCKD-EPI performed worse in patients with an eGFR ≤29 ml/min/1.73m2 (AUC: 0.53) while it was not influenced by higher eGFRs, age, and body size. In contrast, the MDRD equation was accurate only in women (calibration statistics p = 0.72), elderly patients (p = 0.53) and subjects with severe impairment of renal function (p = 0.06) whereas CCG was not significantly biased only in patients between 40 and 59 years (p = 0.6) and with eGFR 45–59 ml/min/1.73m2 (p = 0.32) or ≥ 60 ml/min/1.73m2 (p = 0.48).

Conclusions

In general, CKD-EPI gives the best prediction of death after CABG with unsatisfactory accuracy and calibration only in patients with severe kidney disease. In contrast, the CG and MDRD equations were inaccurate in a clinically significant proportion of patients.
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR
Authors: Li Lei , Zhang Shuai , Li Hao , Chou Haiyan
Published: October 2019

Background

Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma.

Methods

FGFR3 knockdown and overexpression strategies were employed to investigate the effects of FGFR3 on colony formation, cell apoptosis, proliferation, migration, and in vitro invasion, along with the growth and metastasis of melanoma in a xenografts mouse model. The protein expression levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), epidermal growth factor receptor (EGFR), and epithelial-mesenchymal transition (EMT) markers were determined by Western blot analysis.

Results

The mRNA expression of FGFR3 was higher in melanoma tissues than normal healthy tissues. FGFR3 expression in cutaneous malignant melanoma (CMM) tissues was positively correlated with the Breslow thickness and lymph node metastasis. In A357 cells, knockdown of the FGFR3 gene decreased the colony formation ability, cell proliferation, invasion, and migration, but increased the caspase 3 activity and the apoptosis rate; overexpression of FGFR3 increased the colony formation ability, cell proliferation, invasion, and migration, but decreased the caspase 3 activity and apoptosis rates. FGFR3 knockdown also upregulated E-cadherin, downregulated N-cadherin and vimentin, and decreased the phosphorylation levels of ERK, AKT, and EGFR. In the MCC xenografts mice, knockdown of FGFR3 decreased tumor growth and metastasis.

Conclusions

FGFR3, which is highly expressed in CMM tissues, is correlated with increased Breslow thickness and lymph node metastasis. FGFR3 promotes melanoma growth, metastasis, and EMT behaviors, likely by affecting the phosphorylation levels of ERK, AKT, and EGFR.
Clinical analysis of microbiologically proven fungal keratitis according to prior topical steroid use: a retrospective study in South Korea
Authors: Cho Chan-Ho , Lee Sang-Bumm
Published: October 2019

Background

To compare the clinical characteristics and treatment outcomes of microbiologically proven fungal keratitis between users and non-users of prior topical steroids (PS and NPS, respectively).

Methods

Eighty-three cases with microbiologically proven fungal keratitis between January 2000 and December 2016 were reviewed retrospectively. Diagnosis of fungal keratitis was made through potassium hydroxide smear, culture, PCR, or biopsy. Baseline epidemiology, predisposing factors, clinical characteristics, microbiological profiles, and treatment outcomes were evaluated and compared between the PS and NPS groups. Treatment failure was defined as any case with complications or requiring surgery. The risk factors for treatment failure were evaluated using multivariate logistic regression in the overall cohort.

Results

A total of 30 cases with PS group and 53 cases with NPS group were included. Of these, sixteen fungal isolates were identified in the PS group and 14 isolates in the NPS group. Candida was the most common organism in both groups (6 cases, respectively), while Aspergillus (4 cases) was found only in the PS group (p = 0.103). No significant differences were observed in the mean age, sex, occupational distribution, epithelial defect size, hypopyon, and presenting best-corrected visual acuity (BCVA) between the two groups. Differences were observed between the PS and NPS groups in terms of previous ocular surface disease (OSD) (43.3% vs. 22.6%, p = 0.048) and deep infiltration (53.3% vs. 32.1%, p = 0.057). Regarding treatment outcomes, final BCVA < 0.1 (60% vs. 44.2%, p = 0.133), the use of voriconazole (topical 10% vs. 0%, p = 0.044; systemic 23.3% vs. 1.9%, p = 0.003), surgical intervention (43.3% vs. 20.8%, p = 0.029), and treatment failure (46.7% vs. 22.6%, p = 0.023) were more common in the PS group than in the NPS group. The significant risk factors for treatment failure were hypopyon (odds ratio [OR] 6.01, p = 0.005) and deep infiltration (OR 4.38, p = 0.013).

Conclusions

Previous OSD and deep infiltration were more common in the PS group compared to the NPS group. The PS group also experienced worse disease progression and treatment outcomes. These results highlight the need for paying attention to the use of steroids in clinical practice.
Development of questionnaire on awareness and action towards symptoms and risk factors of heart attack and stroke among a Malaysian population
Authors: Ahmed Abdullah Abdulmajid Abdo , AL-Shami Abdulkareem Mohammed , Jamshed Shazia , Fata Nahas Abdul Rahman
Published: October 2019

Background

The awareness of symptoms and action towards heart attack and stroke is important to reduce the morbidity and mortality in both developed and developing countries. The aim of this study was to develop a questionnaire on awareness and action towards symptoms and risk factors of heart attack and stroke among lay public in Malaysia. The questionnaire was developed in both English and Bahasa Melayu.

Methods

Primarily the questions were generated in English. Face and content validity were performed by five experts in Pharmacy Practice and Medicine. A translation as per guidelines into Malay language was performed; followed by face-to-face interview of 96 lay public in Kuantan, Pahang, Malaysia. For internal consistency, reliability was assessed utilizing Cronbach’s alpha.

Results

The mean ± SD of the awareness and action towards heart attack symptoms and risk factors was 65.52 ± 6.3, with a good internal consistency (Cronbach’s alpha = 0.75), whereas the mean of the awareness and action towards stroke symptoms and risk factors was 61.93 ± 7.11, with an accepted internal consistency (Cronbach’s alpha = 0.86).

Conclusion

The current validation research showed that the developed questionnaire is valid and reliable for assessing the awareness and action towards symptoms and risk factors of heart attack and stroke among lay public in Malaysia.
Combined nicotine patch with gum versus nicotine patch alone in smoking cessation in Hong Kong primary care clinics: a randomised controlled trial
Authors: Leung Maria K. W. , Bai Dan , Yip Benjamin H. K. , Fong M. Y. , Lai Petty M. H. , Lai Phoebe , Lai Irene S. Y. , Lam Zoe H. W. , Leung Andrew T. F. , To Dorothy K Y , Wong M. T. , Wong T. K. , Chao David V. K.
Published: October 2019

Background

The prevalence of daily cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however, smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher with combined NRT than single NRT, although local data on safety and benefits of combined NRT are lacking. The aim of this study is to compare the effectiveness of combined NRT with single NRT among HK Chinese.

Methods

This is a one-year, two-arm, parallel randomised trial. Five hundred sixty smokers, who smoked ≥10 cigarettes/day for ≥1 year, were randomized to combined and single NRT. Combined NRT group received counseling and nicotine patch & gum. Single NRT group received counselling and nicotine patch. Primary outcome was abstinence rate measured as self-reported 7-day point prevalence with CO validated at 52 weeks. Secondary outcomes included smoking abstinence rates at 4, 12, & 26 weeks. Crude odds ratio andp-value were reported from logistic regression without adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age, sex, baseline CO and clusters.

Results

Abstinence rates at 4, 12, 26 and 52 weeks were all higher in the combined NRT group (35.8, 21.9, 16.8, 20.1%) compared with the single NRT group (28, 16.8, 11.2, 14.3%). At 4 weeks, combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.00 to 2.05) than the single NRT group. From GEE analysis, combined NRT group had a significantly higher abstinence rate (23.6%) than the single NRT group (17.6%) across repeated measures at all-time points. Combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.15 to 1.77). No significant difference in the side effect profile was detected between groups.

Conclusions

Smokers given 8 weeks of combined NRT were more likely to quit smoking at 4, 12, 26 and 52 weeks compared with single NRT. Combined NRT was as well tolerated as single NRT and it should be further promoted in our community.

Trial registration

NCT03836560 fromClinicalTrial.gov, 9 Feb 2019.
Determinants of neonatal mortality in the largest international border of Brazil: a case-control study
Authors: de Souza Suzana , Duim Etienne , Nampo Fernando Kenji
Published: October 2019

Background

Foz do Iguassu is a Brazilian municipality located in the most populous international border of the country and provides medical care to foreigners. Neonatal mortality in the city is higher than Brazil’s average and corresponds to 61% of all deaths in children under five. The current study aimed to identify the determinants of neonatal mortality in Foz do Iguassu.

Methods

In this case-control study, we analyzed all neonatal deaths occurred in Foz do Iguassu from 2012 to 2016. Birth and mortality data were extracted from two national governmental databases (SINASC and SIM). We extracted data on (i) maternal sociodemographic characteristics, (ii) pregnancy care, and (iii) newborn characteristics. Multiple logistic regression with the conceptual framework was applied to examine the factors associated with neonatal mortality.

Results

Most of the deaths occurred in the early neonatal period (65.9%). The factors associated with neonatal death were fetal congenital anomaly (OR 22.49; CI 95% 7.44–67.95; p = < 0.001); low birth weight (OR 17.15; CI 95% 8.56–34.37; p = < 0.001), first minute Apgar score under 7 (OR 15.60; CI 95% 8.23–29.67; p = < 0.001); zero to 3 prenatal appointments (OR 3.34; CI 95% 1.28–8.73; p = 0.014) and prematurity (OR 3.60; CI 95% 1.87–7.11; p = < 0.001).

Conclusion

The high rate of neonatal death in Foz do Iguassu is strongly associated with newborn characteristics and not associated with maternal sociodemographic characteristics. Thus, the health services in the Brazilian side of this international borders should be aware of the quality of the prenatal care and childbirth attention provided.
Fluoride concentration in ground water and prevalence of dental fluorosis in Ethiopian Rift Valley: systematic review and meta-analysis
Authors: Demelash Habtamu , Beyene Abebe , Abebe Zewdu , Melese Addisu
Published: October 2019

Background

The concentration of fluoride in ground drinking water greater than the world health organization standard value imposes a serious health, social and economic problem in developing countries. In the Ethiopian Rift Valley where deep wells are the major source of drinking water, high fluoride level is expected. Though many epidemiological studies on fluoride concentration and its adverse effects have been conducted in the region, the result is highly scattered and needs systematically summarized for better utilization.

Objective

This research is aimed at estimating the pooled level of fluoride concentration in ground drinking water and the prevalence of dental fluorosis among Ethiopian rift valley residences.

Methods

Cochrane library, MEDLINE/PubMed and Google scholar databases were searched for studies reporting the mean concentration of fluoride in ground water and prevalence of dental fluorosis in Ethiopian Rift valley. Search terms were identified by extracting key terms from reviews and selected relevant papers and review medical subject headings for relevant terms.

Results

The mean fluoride level in ground water and the prevalence of dental fluorosis were pooled from eleven and nine primary studies conducted in Ethiopian Rift Valley respectively. The pooled mean level of fluoride in ground water therefore was 6.03 mg/l (95% CI; 4.72–7.72,p < 0.001) and the pooled prevalence of dental fluorosis among residents in Ethiopian rift valley was 32% (95% CI: 25, 39%,p < 0.001), 29% (95% CI: 22, 36%, p < 0.001) and 24% (95% CI: 17, 32%, p < 0.001 for mild, moderate and sever dental fluorosis respectively. The overall prevalence of dental fluorosis is 28% (95% CI, 24, 32%, p < 0.001).

Conclusions

Though, the concentration level varies across different part of the rift valley region, still the level of fluoride in ground drinking water is greater than the WHO standard value (1.5 mg/l). Relatively high-level pooled prevalence of dental fluorosis was also seen in Ethiopian rift valley. Therefore, further studies covering the temperature, exposure time and other intake path ways with large sample size is recommended. Interventional projects should be implemented to decrease the concentration of fluoride in the ground drinking water source.
Barriers of persistent long-lasting insecticidal nets utilization in villages around Lake Tana, Northwest Ethiopia: a qualitative study
Authors: Malede Asmamaw , Aemero Mulugeta , Gari Sirak Robele , Kloos Helmut , Alemu Kassahun
Published: October 2019

Background

Malaria remains a major public health problem in Ethiopia. The use of LLINs is an effective approach to reducing transmission. Persistent use of LLINs is determined by numerous factors. Quantitative studies have assessed LLIN ownership and utilization, but the behavioral, socio-cultural, socioeconomic and net distribution contexts that impact their use have not been examined in depth. This study aimed to explore barriers of persistent LLIN use among communities around Lake Tana.

Methods

Twenty-three community residents who owned LLINs (15) or not (8) during the study period and 38 key informants were interviewed from April to June 2017. Phenomenological study was employed to explore the local contexts and factors that influence persistent use of LLINs. Individuals were purposefully selected to capture different views. Community residents were selected based on their permanent residence and LLIN use experience. Key informants were health extension workers, local leaders, students, and health professionals. The data were managed using QSR International NVivo Version 10 software and coded, and themes were identified.

Results

Killing ability of nets against arthropods other than mosquitoes reportedly made use of LLINs a favored malaria prevention method despite their ineffectiveness after 3 months. Conical nets were preferred due to their compatibility with varied sleeping structures. Numerous factors influenced persistent use, notably erroneous perceptions about LLINs, malaria and mosquitoes; bedbug infestation; inconvenience; unintended uses; distribution problem of nets; and socio-cultural and economic factors. Unintended uses were often associated with local needs and seldom linked with social issues and deficiencies in information about malaria and LLINs. Collateral benefits were considered important, principally in terms of disinfestation of bedbugs.

Conclusions

Non-persistent LLIN use was associated with inconvenient bed net design and early damage; non-potency of the insecticide against other arthropods; facilitation of bedbug infestation; unintended uses; wrong perceptions about malaria, mosquitoes, and LLINs; and inadequate follow-up regarding LLINs utilization. Distribution of conical nets and provision of adequate information on LLINs and malaria may promote persistent use. Using an insecticide that also kills arthropods other than mosquitoes may reduce unintended uses and increase persistent use.
Neck and shoulder pain among elementary school students: prevalence and its risk factors
Authors: Gheysvandi Elham , Dianat Iman , Heidarimoghadam Rashid , Tapak Leili , Karimi-Shahanjarini Akram , Rezapur-Shahkolai Forouzan
Published: October 2019

Background

Neck and shoulder pain is relatively common among children and teenagers and has a negative impact on their physical and psychological health. This study was carried out to assess the prevalence of neck and shoulder pain among elementary school students, and to investigate the relationship between this pain and its risk factors.

Methods

In this cross-sectional study, 693 elementary school students aged 7 to 12 years from Hamadan city, located in western Iran, were selected through the multistage cluster random sampling method. Data were collected through interviews and questionnaires. For the social and psychological variables, the parent version of the Strengths and Difficulties Questionnaire (SDQ) was used. For assessing each student’s posture, an observational checklist, the Rapid Upper Limbs Assessment (RULA), was used. The data was analyzed using the unadjusted (univariate) and adjusted (multivariate) logistic regression.

Results

The prevalence of the neck pain was slightly higher than that of shoulder pain. The prevalence reported over a month was 35.8 and 30.9% for neck and shoulder pain, respectively. The logistic regression analyses showed that, very high desk height (odds ratio (OR) =1.96, 95% confidence interval CI: 1.02–3.74), backward seat pan inclination (OR = 2.10, 95% CI: 1.37–3.24), forward seat pan inclination (OR = 3.12, 95% CI:1.46–6.68), difficulty in viewing the board (OR = 2.54, 95% CI: 1.10–5.84), too much homework (OR = 2.59, 95% CI: 1.49–4.51), RULA score at level III (OR = 2.88, 95% CI:1.64–5.05), and RULA score at level IV (OR = 3.12, 95% CI: 1.72–5.63) increased the risk of neck pain independently. On the other hand, sitting on desk and seat (OR = 0.59, 95% CI: 0.39–0.91) and laying position for doing homework (OR = 0.53, 95% CI: 0.34–0.81) reduced the related risk. Very short desk height (OR = 2.41, 95% CI: 1.26–4.61) and too much homework (OR = 1.94, 95% CI: 1.10–3.42) increased the risk of shoulder pain.

Conclusion

The elementary school students reported a high prevalence of shoulder and neck pain. This study found that improper sitting positions, as well as physical factors such as the school furniture, too much homework, and difficulty in viewing the classroom board, were associated with pain. Proper interventions considering the risk factors assessed in this study, are suggested.
Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report
Authors: Doubková Martina , Trizuljak Jakub , Vrzalová Zuzana , Hrazdirová Anna , Blaháková Ivona , Radová Lenka , Pospíšilová Šárka , Doubek Michael
Published: October 2019

Background

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous pathological variants in HPS1, HPS3, HPS4, and several other genes lead to clinical manifestation of the disease.

Case presentation

A 57-year-old female was admitted with congenital oculocutaneous albinism, thrombocytopathy and late-onset accelerated pulmonary fibrosis (first symptoms from age 50 onwards). Chest high-resolution computed tomography identified thickening of peribronchovascular interstitium, bronchiectasis, reticulations, honeycombing, ground glass opacities and lung parenchyma consolidations. HPS was clinically suspected. We performed whole exome sequencing (WES), a form of massive parallel sequencing, of proband-parents trio. Whole exome libraries were processed using KAPA Hyper Prep Kit, SeqCap EZ MedExome Enrichment Kit and HyperCap Bead Kit according to the SeqCap EZ HyperCap Workflow. The paired-end 2 × 75 bp sequencing was performed on the Illumina NextSeq 500 Sequencer (Illumina Inc., USA). Furthermore, obtained variants by WES were evaluated using a virtual panel of genes: HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN. We identified a compound heterozygous genotype in HPS1 gene in the proband. We identified a pathogenic frameshift variant c.1189delC; p.(Gln397Serfs*2), resulting in a premature stop codon. This variant has been previously associated with HPS. Furthermore, we characterized previously undescribed nonsense variant c.1507C > T; p.(Gln503*), resulting in a premature stop codon and mRNA degradation through nonsense-mediated decay. Sanger sequencing validated the presence of both variants and simultaneously confirmed the heterozygous carrier status of parents. Unfortunately, the patient died due to fulminant progression of pulmonary fibrosis 2 months after diagnostics.

Conclusions

Compound heterozygous mutations in HPS1 in the proband lead to disruption of HPS1 gene and clinical manifestation of HPS with severe pulmonary fibrosis. This case illustrates the need to consider HPS in differential diagnostics of pulmonary fibrosis. Pulmonary fibrosis is a common cause of death in HPS patients. Earlier diagnosis may enable better treatment for these patients.
Severe community-acquired pneumonia in general medical wards: outcomes and impact of initial antibiotic selection
Authors: Wongsurakiat Phunsup , Chitwarakorn Napat
Published: October 2019

Background

Most international guidelines recommend empirical therapy for community-acquired pneumonia (CAP) to be based on site of care. Some patients with severe CAP are managed in general wards because of limited intensive care unit (ICU) bed or because of unrecognition of the pneumonia severity. Appropriate initial antibiotic treatment for severe CAP outside ICU has not yet been established. This study aimed to determine the prevalence and the impact of initial antibiotic selection on the outcomes of patients with severe CAP who were admitted and managing in general wards.

Methods

This prospective observational study included consecutive patients hospitalized for presumed CAP in general wards over a 1-year period. Severe CAP was identified using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Initial antibiotic treatment in the first 24 h were collected. The primary outcome was the rate of unfavorable outcome (composite outcome of treatment failure and in-hospital death). The secondary outcome was the number of hospital-free days assessed 30 days after enrollment into the study.

Results

There were 94 patients hospitalized with CAP of which 50 (53.2%) patients were compatible with severe CAP. An etiologic diagnosis was found in 43 (45.8%) patients. The most common pathogens identified in patients with severe CAP were Staphylococcus aureus (28.6%) and Klebsiella pneumoniae (28.6%), followed by Pseudomonas aeruginosa (17.9%). Patients with severe CAP had significantly more positive blood culture than patients with non-severe CAP (24% VS 4.5%; p = .008). Initial antibiotic treatment were discordant with the IDSA/ATS guidelines in 42% of all patients hospitalized with CAP, and 52% of patients with severe CAP. Multivariate analysis revealed that age (OR 1.1, 95% CI 1.01–1.1) and initial antibiotic treatment discordant to guidelines for severe CAP in ICU (OR 4.6, 95% CI 1.3–17.1) were independent risk factors of the unfavorable outcome of patients with severe CAP. Patients with unfavorable outcome had lower number of hospital-free days than patients with favorable outcome (5.2 ± 8 days VS 18 ± 7.1 days; p < .001).

Conclusions

Patients with severe CAP outside ICU should be recognized for appropriate initial antibiotic selection to improve outcomes.
The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017
Authors: Osei Albert D. , Mirbolouk Mohammadhassan , Orimoloye Olusola A. , Dzaye Omar , Uddin S. M. Iftekhar , Dardari Zeina A. , DeFilippis Andrew P. , Bhatnagar Aruni , Blaha Michael J.
Published: October 2019

Background

E-cigarette use prevalence has grown rapidly in the US. Despite the popularity of these products, few acute exposure toxicity studies exist, and studies on long-term pulmonary health effects are limited. E-cigarette users who are never combustible cigarette smokers (sole users) constitute a unique group of young adults that may be at increased risk of bronchial hyperreactivity and development of asthma. Given the public health concern about the potential pulmonary health effects of sole e-cigarette use, we aimed to examine the association between e-cigarette use and asthma among never combustible cigarette smokers.

Methods

We pooled 2016 and 2017 data of the Behavioral Risk Factor Surveillance System (BRFSS), a large, cross-sectional telephone survey of adults aged 18 years and older in the U.S. We included 402,822 participants without any history of combustible cigarette smoking (defined as lifetime smoking < 100 cigarettes) and with complete self-reported information on key variables. Current e-cigarette use, further classified as daily or occasional use, was the primary exposure. The main outcome, asthma, was defined as self-reported history of asthma. We assess the relationship of sole e-cigarette use with asthma using multivariable logistic regression adjusting for age, sex, race, income, level of education and body mass index.

Results

Of 402,822 never combustible cigarette smokers, there were 3103 (0.8%) current e-cigarette users and 34,074 (8.5%) with asthma. The median age group of current e-cigarette users was 18–24 years. Current e-cigarette use was associated with 39% higher odds of self-reported asthma compared to never e-cigarette users (Odds Ratio [OR], 1.39; 95% confidence interval: 1.15, 1.68). There was a graded increased odds of having asthma with increase of e-cigarette use intensity. The odds ratio of self-reported asthma increased from 1.31 (95% confidence interval: 1.05, 1.62) in occasional users to 1.73 (95% confidence interval: 1.21, 2.48) in daily e-cigarette users, compared to never e-cigarette users.

Conclusion

Our findings from a large, nationally representative survey suggest increased odds of asthma among never combustible smoking e-cigarette users. This may have potential public health implications, providing a strong rationale to support future longitudinal studies of pulmonary health in young e-cigarette-using adults.
Fewer ischemic strokes, despite an ageing population: stroke models from observed incidence in Norway 2010–2015
Authors: Rand Kim , Dahl Fredrik Andreas , Viana Joe , Rønning Ole Morten , Faiz Kashif Waqar , Barra Mathias
Published: October 2019

Background

Stroke incidence rates have fallen in high-income countries over the last several decades, but findings regarding the trend over recent years have been mixed. The aim of the study was to describe and model temporal trends in incidence of stroke by age and sex between 2010 and 2015 in Norway, and to generate incidence projections towards year 2040.

Methods

All recorded strokes in Norway between 2010 and 2015 were extracted from the National Patient Registry and the National Cause of Death Registry. We report incidence by age, sex, and year; in raw numbers, per 100,000 person-years, by WHO and European standard populations; and generated statistical models by stroke type, age, sex, and year; and projected stroke incidence toward year 2040.

Results

The data covered 30.1 million person-years at risk, 53431 unique individuals hospitalized with a primary stroke diagnosis, and 6315 additional individuals registered as dead due to stroke. From 2010 to 2015, individuals suffering stroke per 100,000 person-years dropped from 239 to 195 (208 to 177 excluding immediate deaths). The decline was driven by ischemic strokes, with a statistically non-significant time trend for hemorrhagic stroke.

Conclusions

The age-dependent incidence of ischemic strokes in Norway is declining rapidly, and more than compensates for the growth and ageing of the population. Comparisons with historic incidence statistics show that the reduction in incidence rates has accelerated over the last two decades.
Infrared spectroscopy coupled to cloud-based data management as a tool to diagnose malaria: a pilot study in a malaria-endemic country
Authors: Heraud Philip , Chatchawal Patutong , Wongwattanakul Molin , Tippayawat Patcharaporn , Doerig Christian , Jearanaikoon Patcharee , Perez-Guaita David , Wood Bayden R.
Published: October 2019

Background

Widespread elimination of malaria requires an ultra-sensitive detection method that can detect low parasitaemia levels seen in asymptomatic carriers who act as reservoirs for further transmission of the disease, but is inexpensive and easy to deploy in the field in low income settings. It was hypothesized that a new method of malaria detection based on infrared spectroscopy, shown in the laboratory to have similar sensitivity to PCR based detection, could prove effective in detecting malaria in a field setting using cheap portable units with data management systems allowing them to be used by users inexpert in spectroscopy. This study was designed to determine whether the methodology developed in the laboratory could be translated to the field to diagnose the presence of Plasmodium in the blood of patients presenting at hospital with symptoms of malaria, as a precursor to trials testing the sensitivity of to detect asymptomatic carriers.

Methods

The field study tested 318 patients presenting with suspected malaria at four regional clinics in Thailand. Two portable infrared spectrometers were employed, operated from a laptop computer or a mobile telephone with in-built software that guided the user through the simple measurement steps. Diagnostic modelling and validation testing using linear and machine learning approaches was performed against the gold standard qPCR. Sample spectra from 318 patients were used for building calibration models (112 positive and 110 negative samples according to PCR testing) and independent validation testing (39 positive and 57 negatives samples by PCR).

Results

The machine learning classification (support vector machines; SVM) performed with 92% sensitivity (3 false negatives) and 97% specificity (2 false positives). The Area Under the Receiver Operation Curve (AUROC) for the SVM classification was 0.98. These results may be better than as stated as one of the spectroscopy false positives was infected by a Plasmodium species other than Plasmodium falciparum or Plasmodium vivax, not detected by the PCR primers employed.

Conclusions

In conclusion, it was demonstrated that ATR-FTIR spectroscopy could be used as an efficient and reliable malaria diagnostic tool and has the potential to be developed for use at point of care under tropical field conditions with spectra able to be analysed via a Cloud-based system, and the diagnostic results returned to the user’s mobile telephone or computer. The combination of accessibility to mass screening, high sensitivity and selectivity, low logistics requirements and portability, makes this new approach a potentially outstanding tool in the context of malaria elimination programmes. The next step in the experimental programme now underway is to reduce the sample requirements to fingerprick volumes.
Ultrasensitive loop mediated isothermal amplification (US-LAMP) to detect malaria for elimination
Authors: Mohon Abu Naser , Getie Sisay , Jahan Nusrat , Alam Mohammad Shafiul , Pillai Dylan R.
Published: October 2019

Background

Malaria elimination requires diagnostic methods able to detect parasite levels well below what is currently possible with microscopy and rapid diagnostic tests. This is particularly true in surveillance of malaria at the population level that includes so-called “asymptomatic” individuals.

Methods

The development of the first ultrasensitive loop mediated amplification method capable of detecting malaria from both whole blood and dried blood spots (DBS) is described. The 18S rRNA and corresponding genes that remain stable on DBS for up to 5 months are targeted.

Results

In the case of Plasmodium falciparum, lower limits of detection of 25 parasite/mL and 50–100 parasite/mL from whole blood and DBS were obtained, respectively. A sensitivity of 97.0% (95% CI 82.5–99.8) and specificity of 99.1% (95% CI 97.6–99.7) was obtained for the detection of all species in asymptomatic individuals from Africa and Asia (n = 494).

Conclusion

This tool is ideally suited for low middle-income countries where malaria is endemic and ultrasensitive surveillance of malaria is highly desirable for elimination.
Association of low-level blood lead with serum uric acid in U.S. adolescents: a cross-sectional study
Authors: Hu Guiping , Jia Guang , Tang Shichuan , Zheng Pai , Hu Lihua
Published: October 2019

Background

Uncertainty remains regarding the association between blood lead levels (BLL) and serum uric acid (SUA) with relatively low BLL exposure because of limited data in the adolescent population. We examined the association between BLL and SUA in U.S. adolescents.

Methods

In this cross-sectional study, 8303 adolescents aged 12–19 years from NHANES 1999–2006 were analyzed. BLL was Ln-transformed for analysis for the skewed distribution. Elevated SUA was defined as ≥5.5 mg/dL. Multivariate linear and multiple logistic regression analyses were performed to evaluate the association of BLL with SUA and elevated SUA. Moreover, a generalized additive model (GAM) and a fitted smoothing curve (penalized spline method) were conducted.

Results

The overall mean BLL was 1.3 μg/dL. Multivariate linear regression analyses showed that LnBLL was independently and positively correlated with SUA level (β = 0.13, 95%CI: 0.09–0.17). Multiple logistic analyses showed that LnBLL was associated with a 24% increased prevalence of elevated SUA (OR = 1.24; 95% CI, 1.11–1.38). Analyses using restricted cubic spline confirmed that the associations of LnBLL with SUA and elevated SUA were linear. Subgroup analyses showed that stronger associations between LnBLL and SUA were detected in adolescents with lower levels of education and estimated glomerular filtration rate (eGFR) (all P for interaction < 0.05).

Conclusions

BLL was independently and positively correlated with SUA level and elevated SUA among U.S. adolescents, particularly with lower levels of education and eGFR. The data suggest that there is no “safe” threshold level of exposure to lead.

Graphical abstract
Radiotherapy for pelvic nodal recurrences after radical prostatectomy: patient selection in clinical practice
Authors: Panje Cedric , Zilli Thomas , Dal Pra Alan , Arnold Winfried , Brouwer Kathrin , Garcia Schüler Helena I. , Gomez Silvia , Herrera Fernanda , Khanfir Kaouthar , Papachristofilou Alexandros , Pesce Gianfranco , Reuter Christiane , Vees Hansjörg , Zwahlen Daniel , Putora Paul Martin
Published: October 2019

Aim

There is no general consensus on the optimal treatment for prostate cancer (PC) patients with intrapelvic nodal oligorecurrences after radical prostatectomy. Besides androgen deprivation therapy (ADT) as standard of care, both elective nodal radiotherapy (ENRT) and stereotactic body radiotherapy (SBRT) as well as salvage lymph node dissection (sLND) are common treatment options. The aim of our study was to assess decision making and practice patterns for salvage radiotherapy (RT) in this setting.

Methods

Treatment recommendations from 14 Swiss radiation oncology centers were collected and converted into decision trees. An iterative process using the objective consensus methodology was applied to assess differences and consensus.

Results

PSMA PET/CT was recommended by 93% of the centers as restaging modality. For unfit patients defined by age, comorbidities or low performance status, androgen deprivation therapy (ADT) alone was recommended by more than 70%. For fit patients with unfavorable tumor characteristics such as short prostate-specific antigen (PSA) doubling time or initial high-risk disease, the majority of the centers (57–71%) recommended ENRT + ADT for 1–4 lesions. For fit patients with favorable tumor characteristics, there were low levels of consensus and a wide variety of recommendations. For 1–4 nodal lesions, focal SBRT was offered by 64% of the centers, most commonly as a 5-fraction course.

Conclusions

As an alternative to ADT, ENRT or SBRT for pelvic nodal oligorecurrences of PC are commonly offered to selected patients, with large treatment variations between centers. The exact number of lymph nodes had a major impact on treatment selection.
Correction to: Emergency surgery due to diaphragmatic hernia: case series and review
Authors: Testini Mario , Girardi Antonia , Isernia Roberta Maria , De Palma Angela , Catalano Giovanni , Pezzolla Angela , Gurrado Angela
Published: October 2019

The original article [1] contains a minor typo in reference 47 (reference [2] in this Correction article); the correct reference notation can be shown in the respective reference within this article.
Model fidelity and team members’ experiences of assertive community treatment in Norway: a sequential mixed-methods study
Authors: Odden Sigrun , Landheim Anne , Clausen Hanne , Stuen Hanne Kilen , Heiervang Kristin Sverdvik , Ruud Torleif
Published: October 2019

Background

Assertive community treatment (ACT) is an evidence-based treatment for people with severe mental illness, and this model is used widely throughout the world. Given the various adaptations in different contexts, we were interested in studying the implementation and adaptation of the ACT model in Norway. The first 12 Norwegian ACT teams were established between 2009 and 2011, and this study investigated the teams’ model fidelity and the team members’ experiences of working with ACT.

Methods

To investigate implementation of the ACT model, fidelity assessments were performed 12 and 30 months after the teams started their work using the Tool for Measurement of Assertive Community Treatment (TMACT). Means and standard deviations were used to describe the ACT teams’ fidelity scores. Cohen’s effect size d was used to assess the changes in TMACT scores from the first to second assessment. Qualitative focus group interviews were conducted in the 12 teams after 30 months to investigate the team members’ experiences of working with the ACT model.

Results

The fidelity assessments of the Norwegian teams showed high implementation of the structural and organizational parts of the ACT model. The newer parts of the model, the recovery and evidence-based practices, were less implemented. Four of the six subscales in TMACT improved from the first to the second assessment. The team members experienced the ACT model to be a good service model for the target population: people with severe mental illness, significant functional impairment, and continuous high service needs. Team members perceived some parts of the model difficult to implement and that it was challenging to find effective ways to collaborate with existing health and social services.

Conclusion

The first 12 Norwegian ACT teams implemented the ACT model to a moderate degree. The ACT model could be implemented in Norway without extensive adaptations. Although the team members were satisfied with the ACT model, especially the results for their service users, inclusion of the ACT team to the existing service system was perceived as challenging.
Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review
Authors: Rostami Dovom Marzieh , Noroozzadeh Mahsa , Mosaffa Nariman , Zadeh–Vakili Azita , Piryaei Abbas , Ramezani Tehrani Fahimeh
Published: October 2019

Background

Development of a hyper-gonadotropic hypoestrogenism condition in women < 40 years, defined as premature ovarian insufficiency (POI), is the most common long-term complication in female survivors of galactosemia. In this systematic review, summarize the galactose (GAL) induced POI in rat and mice models.

Methods

For this systematic review, we conducted a search of case control studies published from 1990 until August 2018 in PubMed/Medline, and Web of science, using the descriptors in the title/abstract field. A ‘pearl growing’ strategy was employed whereby, after obtaining the full text articles, reference lists of all included studies (n = 14) were reviewed for additional publications that could be used.

Results

We selected and categorized 14 studies according to the time of exposure to GAL into two groups of prenatal (n = 4) and postnatal (n = 10). Findings of these studies showed that the different stages of follicular development are targeted differently by galactose exposure during the prenatal and postnatal periods: The small follicles (primordial and primary follicles) are targeted by galactose toxicity during prenatal exposure and the pre-antral and antral follicles are targeted by galactose toxicity during postnatal exposure.

Conclusions

This systematic review shows that galactose has an ovotoxicity effect that can be used to induce appropriate POI animal models only if sufficient doses, proper onset time, and duration of prenatal exposure are taken into account. An optimized model of POI induction should manifest all the required ovarian morphological, hormonal, and estrus cycle changes.
Adjuvant chemotherapy and survival among patients 70 years of age and younger with node-negative breast cancer and the 21-gene recurrence score of 26–30
Authors: Park Seho , Han Yunan , Liu Ying , Toriola Adetunji T. , Peterson Lindsay L. , Colditz Graham A. , Kim Seung Il , Cho Young Up , Park Byeong-Woo , Park Yikyung
Published: October 2019

Background

The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18–30, particularly those with RS 26–30, are not known.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18–30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox’s proportional hazards model.

Results

Among the breast cancer patients with the RS 18–30, 21% of them had RS 26–30. Compared to breast cancer patients with RS 18–25, patients with RS 26–30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26–30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47–0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44–0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor.

Conclusions

The 21-gene RS of 18–30 showed heterogeneous outcomes, and the RS 26–30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26–30 and should be considered for patients, especially younger patients or patients with high-grade tumors.
Correction to: Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial
Authors: van Oostveen Rachel B. , Romero-Palacios Alberto , Whitlock Richard , Lee Shun Fu , Connolly Stuart , Carignan Alex , Mazer C. David , Loeb Mark , Mertz Dominik
Published: October 2019

Following publication of the original article [1], we have been notified of a few mistakes in the “Sample size calculations” section, second paragraph.