bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Diagnosis of Meningococcal Meningitis in a Patient With Familial Mediterranean Fever by the FilmArray Meningitis/Encephalitis Panel: A Case Report
Authors: Ankam Jyoti V. , Torres Sarah , Halse Tanya A. , Canfield Stephen M. , Clynes Neville D. , Thakur Kiran T. , Green Daniel A.
Published: March 2020

Familial Mediterranean fever (FMF) is a rare autoinflammatory disorder of the innate immune system. Patients with innate immune system defects are at a high risk of meningococcal disease, although it is unclear if patients with FMF also have increased susceptibility to invasive infection. Herein, we present a diagnostically challenging case of a male adolescent with a past medical history of FMF stabilized on colchicine who presented with some of the early clinical features of community—acquired bacterial meningitis. To our knowledge, this is the first case of meningococcal meningitis in a patient with FMF diagnosed with the FilmArray Meningitis/Encephalitis (ME) Panel. This case report demonstrates that rapid detection of Neisseria meningitidis by the ME Panel can aid in the early diagnosis and prompt treatment of patients with suspected meningitis and may be the only positive test in patients with early presentation and/or prior antimicrobial therapy.
Is Respiratory Epithelial Adenomatoid Hamartoma Related to Central Compartment Atopic Disease?
Authors: Schertzer Joseph S. , Levy Joshua M. , Wise Sarah K. , Magliocca Kelly R. , DelGaudio John M.
Published: March 2020

Background

Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion of the sinonasal tract that may mimic more concerning pathology. Clinical factors associated with REAH have not been well characterized.

Objective

To report our findings on patients with this pathologic diagnosis.

Methods

A retrospective chart review of patients with REAH between September 2006 and November 2019 was conducted. Data collected included clinical allergic rhinitis and asthma history, additional sinonasal diagnoses, prior sinus surgery, and the location of the REAH within the sinonasal cavity.

Results

Twenty-six patients were identified (53.8% male, mean age 62 years [range, 29–93]). Bilateral REAH occurred in 50%. REAH was located at the superior nasal septum in 84.6% cases, with the remainder identified in sinus contents submitted for pathology, making definitive site uncertain. Concurrent sinonasal inflammatory disorders were identified in 18 patients (69.2%), including chronic rhinosinusitis with nasal polyps—not otherwise specified (6), chronic rhinosinusitis without nasal polyps (4), aspirin-exacerbated respiratory disease (2), allergic fungal rhinosinusitis (1), central compartment atopic disease (5), and IgG4-related sclerosing disease (1). Eight patients had isolated REAH. Adequate allergy records were available for 19 patients, of which 18 of 19 (94.7%) had clinical allergic rhinitis.

Conclusions

REAH is a benign sinonasal lesion commonly located within the central compartment of the nasal cavity, a site of significant allergen exposure. Affected patients have a high incidence of allergy along with chronic inflammatory conditions. The coexistence of REAH within inflammatory nasal mucosa in a consistent anatomic location, suggests REAH may have a similar etiology to central compartment atopic disease, with resultant respiratory glandular ingrowth within long-standing reactive changes of mucosa derived from ethmoid embryologic origin.
Sex differences in the agreement between left ventricular ejection fraction measured by myocardial perfusion scintigraphy and by echocardiography
Authors: Jaker Sams , Burgan Amjad , Prakash Vineet , Birkinshaw Alexander , Moosai Kishan , Jacques Adam , Fluck David , MacGregor Mark , Lazariashvili Otar , Sharma Pankaj , Fry Christopher H , Han Thang S
Published: March 2020

Background

Left ventricular ejection fraction (LVEF) is generally measured by echocardiography but is increasingly available with myocardial perfusion scintigraphy. With myocardial perfusion scintigraphy, the threshold of LVEF below which there is a risk for myocardial infarct or sudden cardiac death is higher for women (51%) than for men (43%). We tested the hypothesis that such a sex difference may also occur with echocardiography and myocardial perfusion scintigraphy.

Methods

Four hundred and four men, mean age = 67.7 ± SD = 12.3 yr; 339 women, 67.7 ± 11.7 yr had separate myocardial perfusion scintigraphy and echocardiography examinations within six months. A subset of 327 of these patients (181 men, 68.8 ± 12.1 yr; 146 women, 66.4 ± 12.1 yr) had examinations within one month and were additionally analysed as this sub-group. Myocardial perfusion scintigraphy and echocardiography were used to measure LVEF at rest and their agreement (neither considered as a reference method) was assessed by Bland–Altman plots: LVEF difference (myocardial perfusion scintigraphy minus echocardiography ) against average LVEF ([Formula: see text]).

Results

Of patients who had myocardial perfusion scintigraphy and echocardiography performed within six months, mean LVEF difference = +1.1% (95% limits of agreement: −19.3 to +21.6) in men but +10.9% (−10.7 to +32.5) in women. LVEF difference diverged from zero marginally in men (mean difference = +1.1, 95%CI  = +0.1 to +2.1, p =  0.028) but more in women (+10.9, +9.8 to +12.1, p < 0.001). The LVEF difference correlated with average LVEF itself in both men ( r =  0.305, p < 0.001) and women ( r =  0.361, p < 0.001), and with age in women ( r = 0.117, p = 0.031). Similar results were observed for the subset.

Conclusions

Caution should be taken when interpreting LVEF measured by different techniques due to their wide limits of agreement and systematic bias, more markedly in women.
Potential Opioid-Related Adverse Drug Events Are Associated With Decreased Revenue in Hip Replacement Surgery in the Older Population
Authors: Baker Justin , Brovman Ethan Y. , Rao Nikhilesh , Beutler Sascha S. , Urman Richard D.
Published: March 2020

Introduction:

Opioid-related adverse drug events (ORADEs) are an increasingly recognized complication associated with the common prescription of opioids after orthopedic surgery. In this study, we attempted to understand how potential ORADEs following hip replacement surgery in older patients affected hospital length of stay, hospital revenue, and their association with specific risk factors and clinically relevant diseases occurring during hospitalization.

Methods:

We conducted a retrospective study using the Centers for Medicare and Medicaid Services Administrative Database to analyze Medicare discharges after hip replacement surgery to identify potential ORADEs. The impact of potential ORADEs on mean hospital length of stay (LOS) and hospital revenue was analyzed.

Results:

The potential ORADE rate in patients who underwent hip replacement surgery was 8.6%. The mean LOS for discharges with a potential ORADE was 1.41 days longer than that for discharges without an ORADE. The mean hospital revenue per day with a potential ORADE was US$1708 less than without an ORADE. Potential ORADEs were also found to be strongly associated with poor patient outcomes such as pneumonia, septicemia, and shock.

Discussion:

Potential ORADEs in hip replacement surgery in older patients are associated with longer hospitalizations, decreased hospital revenue per day, certain patient risk factors, and clinically relevant diseases occurring during hospitalizations. Our finding of an association between potential ORADEs and decreased hospital revenue per day may be attributed to the management of these adverse events, as a patient may need to undergo additional testing, may need additional treatment regimens, and may need a higher level of care.

Conclusion:

By reducing the use of opioids and employing a multimodal analgesic approach, we may improve patient care, decrease hospital lengths of stay, and increase hospital revenue
Utilization of Offset Iliac Connectors as Anchoring Sites in Severe Rigid Scoliosis: New Technique
Authors: Barakat Ahmed , Mansy Yasser El , Saghir Hesham El
Published: March 2020

Study Design:

This was a prospective cohort study.

Objectives:

To introduce the iliac connectors as fixation options in spinal constructs used for correction of severe scoliosis at locations other than the lumbopelvic region.

Methods:

Nine patients with severe rigid scoliosis undergoing surgical release and posterior instrumentation in the period between January 2013 and January 2015 were included in this prospective cohort study. Mean age was 18.4 years; 8 had triple structural curves, and the remaining patient had double structural curves. Cobb angles of the primary and compensatory curves were compared with the immediate, 1-year, and 2-year postoperative measurements using the F test, with P value ≤.05 indicating statistical significance. Screw densities of the final constructs were calculated and compared with the screw densities when the offset iliac connectors were not used.

Results:

One to 4 offset iliac connectors were used in all 9 patients, increasing screw density by a mean of 6.24 ( P < .001). The mean Cobb angle of the major curve was corrected from 98.44° to 58.2° ( P < .001), that of the first compensatory curve, from 56.55° to 38.33° ( P < .001), and that of the second compensatory curve, from 40.75° to 26.63° ( P < .001). There were no intraoperative neurological complications. After a mean follow-up of 30.6 months, the construct remained stable in all patients with no loss of correction.

Conclusion:

Offset iliac connectors can be a valuable tool to increase screw density in correction of severe scoliosis, thus increasing overall biomechanical strength of the final construct.
Interplay of Culture and Horticulture Among the Savara of Andhra Pradesh, India
Authors: Sharma B. V. , J. Gopika
Published: March 2020

The perception that communities are passive recipients of innovations has long been rejected. The way communities respond to any innovation is the result of unique and complex negotiations and renegotiations between their culture and the innovations. These responses can cause changes in the existing elements of the culture and lead to the emergence of new elements that act as feedback into the initial process. It is from this perspective that this article aims to understand the introduction and expansion of horticulture among the Savara of Seethampeta Mandal, Andhra Pradesh. The interplay of the Savara culture and horticulture is grounded on certain Savara institutions and their responses to the innovation of horticulture, creating a loop where positive responses from the earlier culture feed into new elements of culture that are positively oriented towards horticulture. Using ethnographic data based on fieldwork, this article seeks to understand how the earlier and emergent Savara cultures have facilitated the widespread adoption of horticulture in the area under study.
Comparison of periarticular multidrug infiltration and epidural catheter use in total knee arthroplasty: A prospective randomized controlled study
Authors: Ukai Taku , Kosuke Hamahashi , Ebihara Goro , Watanabe Masahiko
Published: March 2020

Purpose:

The purpose of this study was to assess the effectiveness of periarticular multidrug infiltration (PMDI) and compare it with that of epidural catheter use.

Methods:

Fifty-eight patients (58 joints) who underwent total knee arthroplasty were included in this single-center, prospective, parallel, randomized, controlled trial. Preoperatively, patients were randomly categorized into the PMDI and epidural catheter groups. We evaluated postoperative pain (visual analog scale (VAS) and narcotic consumption), functional outcomes (range of motion (ROM) of knee flexion, the day patients could perform the straight-leg raising (SLR) test, and day of starting cane use), and laboratory data (white blood cell (WBC) and C-reactive protein (CRP)).

Results:

There was no significant difference in the VAS score, ROM of knee flexion, the day patients could do SLR, and the day of starting cane use between the PMDI and epidural catheter groups. However, the PMDI group could perform SLR on a postoperative day (POD) 1 ( p < 0.05). WBC level on POD 1 was significantly higher in the PMDI group ( p < 0.05), whereas the CRP levels on POD 1 ( p < 0.01), 3 ( p < 0.01), and 5 ( p < 0.01) were significantly lower in the PMDI group than in the epidural catheter group. The frequency of side effects was not significantly different between the groups.

Conclusion:

PMDI was as effective as epidural catheter use for pain control. A higher percentage of patients who underwent PMDI could perform SLR on POD 1; therefore, the functional recovery was earlier in the PMDI group than in the epidural catheter group. PMDI may suppress inflammation in the whole body because of steroids.
Platelet-Rich Plasma Is an Equal Alternative to Surgery in the Treatment of Type 1 Medial Epicondylitis
Authors: Bohlen Hunter L. , Schwartz Zachary E. , Wu Victor J. , Thon Stephen G. , Finley Zachary J. , O’Brien Michael J. , Savoie Felix H.
Published: March 2020

Background:

Medial epicondylitis (ME) is characterized as an overuse injury resulting in pathological alterations of the common flexor tendon at the elbow. Platelet-rich plasma (PRP) has recently become of interest in the treatment of musculoskeletal conditions as an alternative to operative management.

Purpose:

To compare the outcomes of recalcitrant type 1 ME after treatment with either PRP or surgery.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

To compare the 2 methods of treatment, we performed a retrospective review of 33 patients diagnosed with type 1 ME from 2006 to 2016 with a minimum clinical follow-up of 1 year who had failed an initial nonoperative treatment program of injections, medication, topical creams, and/or physical therapy. Overall, 15 patients were treated with a series of 2 leukocyte-rich PRP injections, and 18 patients were treated with surgery. Outcome measures included time to pain-free status, time to full range of motion (ROM), the Mayo Elbow Performance Score (MEPS), and the Oxford Elbow Score (OES). Each patient had at least 1-year follow-up. They were then contacted by telephone to determine final scores at a minimum 2-year follow-up. Unsuccessful outcomes were determined by the Nirschl grading system and failure to reach pain-free status, achieve baseline ROM, or return to previous activity.

Results:

The mean final follow-up was 3.9 years. A statistically significant improvement was noted in both time to full ROM (42.3 days for PRP vs 96.1 days for surgery; P < .01) and time to pain-free status (56.2 days for PRP vs 108.0 days for surgery; P < .01). Successful outcomes were observed in 80% of patients treated with PRP and 94% of those treated operatively ( P = .37). No significant difference was found in return-to-activity rates, overall successful outcomes, MEPS scores, or OES scores.

Conclusion:

In this case series, the use of PRP showed clinically similar outcomes to those of surgery in recalcitrant type 1 ME. PRP can be considered as an alternative to surgery in the treatment of recurrent ME, with an earlier time to full ROM and time to pain-free status compared with surgery.
Factors That Influence the Relationship Between Social Support and Health-Related Quality of Life of Older People Living in the Community
Authors: Sarla Efstathia , Lambrinou Ekaterini , Galanis Petros , Kalokairinou Athena , Sourtzi Panayota
Published: March 2020

As the proportion of older people in Greece grows and the need for promoting healthy aging is apparent, it becomes increasingly important to investigate the relationship between social support and health-related quality of life (HRQoL) of older people in the community. A cross-sectional study was conducted in 451 older people living in the community in greater Athens, Greece, with an anonymous questionnaire, including demographics, and the EQ5D including EuroQol–visual analogue scale (EQ-VAS) and the Multidimensional Scale of Perceived Social Support. Multivariate linear regression analysis was applied to identify independent factors related to perceived social support and HRQoL. The majority of older people were women, married or widowed, living with their family or alone. Perceived social support was medium and higher from significant others and family. A statistically significant positive relationship was found between social support from significant others/friends and HRQoL, as well as between social support from friends/family/significant others and EQ-VAS. In conclusion, HRQoL of older people is influenced by the received social support.
Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional study of adult patients by ILROG
Authors: Binkley Michael S. , Rauf M. Shahzad , Milgrom Sarah A. , Pinnix Chelsea C. , Tsang Richard , Dickinson Michael , Ng Andrea K. , Roberts Kenneth B. , Gao Sarah , Balogh Alex , Ricardi Umberto , Levis Mario , Casulo Carla , Stolten Michael , Specht Lena , Plastaras John P. , Wright Christopher , Kelsey Christopher R. , Brady Jessica L. , Mikhaeel N. George , Hoppe Bradford S. , Terezakis Stephanie A. , Picardi Marco , Della Pepa Roberta , Kirova Youlia , Akhtar Saad , Maghfoor Irfan , Koenig Julie L. , Jackson Christopher , Song Erin , Sehgal Shuchi , Advani Ranjana H. , Natkunam Yasodha , Constine Louis S. , Eich Hans T. , Wirth Andrew , Hoppe Richard T.
Published: March 2020

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.
Research on a stock-matching trading strategy based on bi-objective optimization
Authors: Diao Haican , Liu Guoshan , Zhu Zhuangming
Published: March 2020

In recent years, with strict domestic financial supervision and other policy-oriented factors, some products are becoming increasingly restricted, including nonstandard products, bank-guaranteed wealth management products, and other products that can provide investors with a more stable income. Pairs trading, a type of stable strategy that has proved efficient in many financial markets worldwide, has become the focus of investors. Based on the traditional Gatev–Goetzmann–Rouwenhorst (GGR, Gatev et al., 2006) strategy, this paper proposes a stock-matching strategy based on bi-objective quadratic programming with quadratic constraints (BQQ) model. Under the condition of ensuring a long-term equilibrium between paired-stock prices, the volatility of stock spreads is increased as much as possible, improving the profitability of the strategy. To verify the effectiveness of the strategy, we use the natural logs of the daily stock market indices in Shanghai. The GGR model and the BQQ model proposed in this paper are back-tested and compared. The results show that the BQQ model can achieve a higher rate of returns.
Early detection of viable Francisella tularensis in environmental matrices by culture-based PCR
Authors: Buse Helen Y. , Morris Brian J. , Rice Eugene W.
Published: March 2020

Background

Francisella tularensis is a fastidious, Gram-negative coccobacillus and is the causative agent of tularemia. To assess viability yet overcome lengthy incubation periods, a culture-based PCR method was used to detect early growth of the lowest possible number of F. tularensis cells. This method utilized a previously developed enhanced F. tularensis growth medium and is based on the change in PCR cycle threshold at the start and end of each incubation.

Results

To test method robustness, a virulent Type A1 (Schu4) and B (IN99) strain and the avirulent Live Vaccine Strain (LVS) were incubated with inactivated target cells, humic acid, drinking and well water, and test dust at targeted starting concentrations of 1, 10, and 100 CFU mL− 1 (low, mid, and high, respectively). After 48 h, LVS growth was detected at all targeted concentrations in the presence of 106 inactivated LVS cells; while Schu4 and IN99 growth was detected in the presence of 104 Schu4 or IN99 inactivated cells at the mid and high targets. Early detection of F. tularensis growth was strain and concentration dependent in the presence of fast-growing well water and test dust organisms. In contrast, growth was detected at each targeted concentration by 24 h in humic acid and drinking water for all strains.

Conclusions

Results indicated that the culture-based PCR assay is quick, sensitive, and specific while still utilizing growth as a measure of pathogen viability. This method can circumvent lengthy incubations required for Francisella identification, especially when swift answers are needed during epidemiological investigations, remediation efforts, and decontamination verification.
The use of electronic healthcare records for colorectal cancer screening referral decisions and risk prediction model development
Authors: Cooper Jennifer Anne , Ryan Ronan , Parsons Nick , Stinton Chris , Marshall Tom , Taylor-Phillips Sian
Published: March 2020

Background

The database used for the NHS Bowel Cancer Screening Programme (BCSP) derives participant information from primary care records. Combining predictors with FOBTs has shown to improve referral decisions and accuracy. The richer data available from GP databases could be used to complement screening referral decisions by identifying those at greatest risk of colorectal cancer. We determined the availability of data for key predictors and whether this information could be used to inform more accurate screening referral decisions.

Methods

An English BCSP cohort was derived using the electronic notifications received from the BCSP database to GP records. The cohort covered a period between 13th May 2009 to 17th January 2017. Completeness of variables and univariable associations were assessed. Risk prediction models were developed using Cox regression and multivariable fractional polynomials with backwards elimination. Optimism adjusted performance metrics were reported. The sensitivity and specificity of a combined approach using the negative FOBT model plus FOBT positive patients was determined using a probability equivalent to a 3% PPV NICE guidelines level.

Results

292,059 participants aged 60–74 were derived for the BCSP screening cohort. A model including the screening test result had a C-statistic of 0.860, c-slope of 0.997, and R2 of 0.597. A model developed for negative screening results only had a C-statistic of 0.597, c-slope of 0.940, and R2 of 0.062. Risk predictors included in the models included; age, sex, alcohol consumption, IBS diagnosis, family history of gastrointestinal cancer, smoking status, previous negatives and whether a GP had ordered a blood test. For the combined screening approach, sensitivity increased slightly from 53.90% (FOBT only) to 58.82% but at the expense of an increased referral rate.

Conclusions

This research has identified several potential predictors for CRC in a BCSP population. A risk prediction model developed for BCSP FOBT negative patients was not clinically useful due to a low sensitivity and increased referral rate. The predictors identified in this study should be investigated in a refined algorithm combining the quantitative FIT result. Combining data from multiple sources enables fuller patient profiles using the primary care and screening database interface.
Lifetime patient outcomes and healthcare utilization for Bronchopulmonary dysplasia (BPD) and extreme preterm infants: a microsimulation study
Authors: van Katwyk Sasha , Augustine Sajit , Thébaud Bernard , Thavorn Kednapa
Published: March 2020

Background

Bronchopulmonary dysplasia (BPD) is among the most severe chronic lung diseases and predominantly affects premature infants. There is a general understanding of BPD’s significant impact on the short-term outcomes however there is little evidence on long-term outcomes. Our study estimates the lifetime clinical outcomes, quality of life, and healthcare costs of BPD and associated complications.

Methods

We developed a microsimulation model to estimate lifetime clinical and economic burden of BPD among extreme preterm infants (≤28 weeks gestational age at birth) and validated it against the best available Canadian data. We further estimate the cumulative incidence of major complications associated with BPD, differentiated by BPD severity and gestational age category.

Results

We find, on average, patients with BPD and resulting complications will incur over CAD$700,000 in lifetime health systems costs. We also find the average life expectancy of BPD patients to be moderately less than that of the general population and significant reductions in quality-adjusted life year due to major complications. Healthcare utilization and quality of life measures vary dramatically according to BPD severity, suggesting significant therapeutic headroom for interventions that can prevent or mitigate the effects of BPD for patients.

Conclusions

Our study adds a significant expansion of existing evidence by presenting the lifetime burden of BPD based on key patient characteristics. Given the extreme cost burden at the earliest stage of life and lifetime negative impact on quality of life, there is larger headroom for investment in prevention and mitigation of severe BPD than is currently available.
Rare and common variants analysis of the EMB gene in patients with schizophrenia
Authors: Zhou Juan , Ma Chuanchuan , Wang Ke , Li Xiuli , Zhang Han , Chen Jianhua , Li Zhiqiang , Shi Yongyong
Published: March 2020

Background

Recent genome-wide association study showed rs10940346 locus near EMB gene was significantly associated with schizophrenia and suggested that EMB gene is one of the potentially causal genes for schizophrenia, but no causal variant has been identified. Our study aims to further verify EMB gene is a susceptibility gene for schizophrenia and to identify potentially causal variants in EMB gene that lead to schizophrenia.

Methods

Targeted sequencing for the un-translated region and all exons of EMB gene was performed among 1803 patients with schizophrenia and 997 healthy controls recruited from Chinese Han population.

Results

A total of 58 high-quality variants were identified in case and control groups. Seven of them are nonsynonymous rare variations, EMB: p.(Ala52Thr), p.(Glu66Gly), p.(Ser93Cys), p.(Ala118Val), p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), but none of them reached statistical significance. Among them, p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), were predicted to be deleterious variants. In addition, a common variant, rs3933097 located in 3′-UTR of EMB gene, achieved allelic and genotypic significance with schizophrenia (Pallele = 3.82 × 10− 6, Pgenotype = 3.18 × 10− 5).

Conclusions

Our research first presented a comprehensive mutation spectrum of exons and un-translated region in EMB gene for schizophrenia and provided additional evidence of EMB gene being a susceptibility gene for schizophrenia. However, further functional validations are necessary to reveal its role in the etiology of schizophrenia.
Measuring quality of life in life-threatening illness – content validity and response processes of MQOL-E and QOLLTI-F in Swedish patients and family carers
Authors: Axelsson Lena , Alvariza Anette , Carlsson Nina , Cohen S. Robin , Sawatzky Richard , Årestedt Kristofer
Published: March 2020

Background

The McGill Quality of Life Questionnaire - Expanded (MQOL-E) and the Quality of Life in Life-Threatening Illness-Family Carer/Caregiver version (QOLLTI-F) are developed for use with patients facing the end of life and their family carers, respectively. They are also developed for possible use as companion instruments. Contemporary measurement validity theory places emphasis on response processes, i.e. what people feel and think when responding to items. Response processes may be affected when measurement instruments are translated and adapted for use in different cultures. The aim of this study was to translate and examine content validity and response processes during completion of MQOL-E and QOLLTI-F version 2 (v2) among Swedish patients with life-threatening illness and their family carers.

Methods

The study was conducted in two stages (I) translation and adaptation (II) examination of content validity and response processes using cognitive interviews with 15 patients and 9 family carers. Participants were recruited from the hemodialysis unit, heart clinic, lung clinic and specialized palliative care of a Swedish county hospital. Patients had life-threatening illness such as advanced heart failure, advanced chronic obstructive pulmonary disease, end-stage kidney disease or advanced cancer. Patients were outpatients, inpatients or receiving home care.

Results

Patients and family carers respectively believed that the items of the MQOL-E and QOLLTI-F v2 reflect relevant and important areas of their quality of life. Although some items needed more time for reflection, both instruments were considered easy to understand. Some changes were made to resolve issues of translation. Participants expressed that reflecting on their situation while answering questions was valuable and meaningful to them, and that responding was an opportunity to express feelings.

Conclusions

The results of response processes pertaining to the Swedish translations of both MQOL-E and QOLLTI-F v2 contribute evidence regarding content validity, linguistic equivalence and cultural appropriateness of the translated instruments. In addition, results show that the instruments may support conversations on matters of importance for quality of life between patients and/or family carers and health care professionals. Further research is needed to study the psychometric properties of Swedish translations.
Psychometric properties of the Czech Integrated Palliative Outcome Scale: reliability and content validity analysis
Authors: Vlckova Karolina , Hoschlova Eva , Chroustova Eva , Loucka Martin
Published: March 2020

Background

Outcome measurement is an essential part of the evaluation of palliative care and the measurements need to be reliable, valid and adapted to the culture in which they are used. The Integrated Palliative Outcome Scale (IPOS) is a widely used tool for assessing personal-level outcomes in palliative care. The aim of this study was to provide Czech version of IPOS and assess its psychometric properties.

Methods

Patients receiving palliative care in hospice or hospitals completed the IPOS. The reliability of Czech IPOS was tested with Cronbach alpha (for internal consistency), the intraclass correlation coefficient for total IPOS score and weighted Kappa (for test-retest reliability of individual items). Factor analysis was used for elucidating the construct (Exploratory Factor Analysis). Convergent validity was tested with correlation analysis (Spearman correlation) in a part of the sample, who completed also the Edmonton Symptom Assessment System (ESAS) and the Palliative Performance Scale (PPS).

Results

The sample consisted of 140 patients (mean age 72; 90 women; 81% oncological disease). The Cronbach alpha was 0.789; intraclass correlation was 0.88. The correlations of IPOS with ESAS was R = 0.4 and PPS R = − 0.2. Exploratory factor analysis revealed a 2-factor solution on our data. The first factor covers emotional and information needs and the second factor covers physical symptoms.

Conclusion

Czech IPOS has very good reliability regarding both internal consistency and test-retest reliability. Together with an item analysis results, we can conclude that the Czech adaptation of the tool was successful. The convergent validity needs to be assessed on the larger sample and the proposed 2-factor internal structure of the questionnaire has to be confirmed by using CFA.
Evaluating the performance of a low-cost mobile phone attachable microscope in cervical cytology
Authors: Naqvi Ali , Manglik Niti , Dudrey Ellen , Perry Cynthia , Mulla Zuber D. , Cervantes Jorge L.
Published: March 2020

Background

Cervical cancer remains a global health problem especially in remote areas of developing countries which have limited resources for cervical cancer screening. In this study, we evaluated the performance of a low-cost, smartphone attachable paper-based microscope when used for classifying images of cervical cytology.

Methods

Cervical cytology samples included: 10 Normal, 10 Low-grade squamous intraepithelial lesion (LSIL), 10 High-grade squamous intraepithelial lesion (HSIL), and 10 Malignant Pap Smears. The agreement between conventional microscopy vs. Foldscope imaging was calculated using a weighted kappa coefficient. A confusion matrix was created with three classes: Normal, LSIL, and HSIL/malignant, to evaluate the performance of the Foldscope by calculating the accuracy, sensitivity, and specificity.

Results

We observed a kappa statistic of 0.68 for the agreement. This translates into a substantial agreement between the cytological classifications by the Foldscope vs. conventional microscopy. The accuracy of the Foldscope was 80%, with a sensitivity and specificity of 85 and 90% for the HSIL/Mal category, 80 and 83.3%, for LSIL, and 70 and 96.7% for Normal.

Conclusions

This study highlights the usefulness of the Foldscope in cervical cytology, demonstrating it has substantial agreement with conventional microscopy. Its use could improve cytologic interpretations in underserved areas and, thus, improve the quality of cervical cancer screening. Improvements in existing limitations of the device, such as ability to focus, could potentially increase its accuracy.
Healthcare utilization and out-of-pocket expenditures associated with depression in adults: a cross-sectional analysis in Nepal
Authors: Rajan Selina , Rathod Sujit D. , Luitel Nagendra P. , Murphy Adrianna , Roberts Tessa , Jordans Mark J. D.
Published: March 2020

Background

Despite attempts to improve universal health coverage (UHC) in low income countries like Nepal, most healthcare utilization is still financed by out-of-pocket (OOP) payments, with detrimental effects on the poorest and most in need. Evidence from high income countries shows that depression is associated with increased healthcare utilization, which may lead to increased OOP expenditures, placing greater stress on families. To inform policies for integrating mental healthcare into UHC in LMIC, we must understand healthcare utilization and OOP expenditure patterns in people with depression. We examined associations between symptoms of depression and frequency and type of healthcare utilization and OOP expenditure among adults in Chitwan District, Nepal.

Methods

We analysed data from a population-based survey of 2040 adults in 2013, who completed the PHQ-9 screening tool for depression and answered questions about healthcare utilization. We examined associations between increasing PHQ-9 score and healthcare utilization frequency and OOP expenditure using negative binomial regression. We also compared utilization of specific outpatient service providers and their related costs among adults with and without probable depression, determined by a PHQ-9 score of 10 or more.

Results

We classified 80 (3.6%) participants with probable depression, 70.9% of whom used some form of healthcare in the past year compared to 43.9% of people without probable depression. Mean annual OOP healthcare expenditures were $118 USD in people with probable depression, compared to $110 USD in people without. With each unit increase in PHQ-9 score, there was a 14% increase in total healthcare visits (95% CI 7–22%,p < 0.0001) and $9 USD increase in OOP expenditures (95% CI $2–$17;p < 0.0001). People with depression sought most healthcare from pharmacists (30.1%) but reported the greatest expenditure on specialist doctors ($36 USD).

Conclusions

In this population-based sample from Central Nepal, we identified dose-dependent increases in healthcare utilization and OOP expenditure with increasing PHQ-9 scores. Future studies should evaluate whether provision of mental health services as an integrated component of UHC can improve overall health and reduce healthcare utilisation and expenditure, thereby alleviating financial pressures on families.
“We’ve got the home care data, what do we do with it?”: understanding data use in decision making and quality improvement
Authors: Elliott Jacobi , Gordon Alicia , Tong Catherine E. , Stolee Paul
Published: March 2020

Background

In the past decade the provision of home care services in Canada has doubled; with this increase there has been a growing interest in improving quality and safety. National-level data are captured in the Home Care Reporting System (HCRS), using the interRAI-HC tools. Data in the HCRS provide decision-makers and administrators with actionable evidence to inform quality and safety improvement initiatives. The objective of this study was to determine how providers and administrators were using these data, and if there were any opportunities to enhance their use.

Methods

We collaborated with the Canadian Patient Safety Institute to conduct this qualitative study. To understand data use in home care, we recruited participants in management and/or data analysis roles from home care organizations across Canada. We conducted three individual interviews and three focus group interviews with a total of eleven participants from five Canadian provinces. Individual and focus group interviews were audio recorded, transcribed, and analysed using a combination of emergent coding and thematic analysis.

Results

Several participants provided powerful examples of how interRAI data have been used to guide patient safety and quality improvement initiatives; however, all participants recognized challenges in using these data. Leveraging interRAI data in the complex home care environment is limited by several factors: the general “newness” of these data in many jurisdictions; the sheer volume of data; limited capacity and resources to interpret and analyse the data; and connectivity issues in rural areas. Participants recognized and appreciated the training that has been provided, and made several recommendations for additional training.

Conclusions

Mandated clinical datasets, such as the suite of interRAI tools, have the potential to improve quality and inform decision-making. However, in order to utilize these data, home care agencies require additional education, personnel and supports. Additional training and resources for these organizations could improve the use of available data by home care agencies, as well as outcomes for individuals receiving home care services.
Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1
Authors: Gu Chunming , Yin Zhao , Nie Hong , Liu Yanjun , Yang Juhua , Huang Guiping , Shen Jianping , Chen Liguo , Fei Jia
Published: March 2020

Background

Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM.

Results

Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity.

Conclusions

In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.
Expression of Concern to: Drug metabolite synthesis by immobilized human FMO3 and whole cell catalysts
Authors: Gao Chongliang , Zheng Tingjie
Published: March 2020

Expression of Concern.
Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression
Authors: Liang Gehao , Ling Yun , Mehrpour Maryam , Saw Phei Er , Liu Zihao , Tan Weige , Tian Zhenluan , Zhong Wenjing , Lin Wanyi , Luo Qing , Lin Qun , Li Qiufang , Zhou You , Hamai Ahmed , Codogno Patrice , Li Jun , Song Erwei , Gong Chang
Published: March 2020

Background

Although both circular RNAs (circRNAs) and autophagy are associated with the function of breast cancer (BC), whether circRNAs regulate BC progression via autophagy remains unknown. In this study, we aim to explore the regulatory mechanisms and the clinical significance of autophagy-associated circRNAs in BC.

Methods

Autophagy associated circRNAs were screened by circRNAs deep sequencing and validated by qRT-PCR in BC tissues with high- and low- autophagic level. The biological function of autophagy associated circRNAs were assessed by plate colony formation, cell viability, transwells, flow cytometry and orthotopic animal models. For mechanistic study, RNA immunoprecipitation, circRNAs pull-down, Dual luciferase report assay, Western Blot, Immunofluorescence and Immunohistochemical staining were performed.

Results

An autophagy associated circRNA circCDYL was elevated by 3.2 folds in BC tissues as compared with the adjacent non-cancerous tissues, and circCDYL promoted autophagic level in BC cells via the miR-1275-ATG7/ULK1 axis; Moreover, circCDYL enhanced the malignant progression of BC cells in vitro and in vivo. Clinically, increased circCDYL in the tumor tissues and serum of BC patients was associated with higher tumor burden, shorter survival and poorer clinical response to therapy.

Conclusions

circCDYL promotes BC progression via the miR-1275-ATG7/ULK1-autophagic axis and circCDYL could act as a potential prognostic and predictive molecule for breast cancer patients.
Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes
Authors: Thomson Carolyn A. , McColl Alison , Graham Gerard J. , Cavanagh Jonathan
Published: March 2020

Background

Recent years have seen an explosion of research pertaining to biological psychiatry, yet despite subsequent advances in our understanding of neuroimmune communication pathways, how the brain senses and responds to peripheral inflammation remains poorly understood. A better understanding of these pathways may be important for generating novel therapeutics to treat many patients with chronic inflammatory diseases who also suffer from neuropsychiatric comorbidities. Here we have systematically assessed the leukocyte infiltrate to the brain following systemic endotoxin exposure to better understand this novel route of neuroimmune communication.

Methods

Mice were injected intraperitoneally with LPS daily for 2, 5 or 7 consecutive days. We systematically interrogated the subsequent induction of chemokine transcription in the brain using TaqMan low-density arrays. A combination of flow cytometry and immunohistochemistry was then used to characterise the accompanying leukocyte infiltrate.

Results

Repeated LPS challenges resulted in prolonged activation of brain-resident microglia, coupled with an increased local transcription of numerous chemokines. After 2 days of administering LPS, there was a marked increase in the expression of the neutrophil chemoattractants CXCL1 and CXCL2; the monocyte chemoattractants CCL2, CCL5, CCL7 and CCL8; and the lymphocyte chemoattractants CXCL9, CXCL10 and CXCL16. In a number of cases, this response was sustained for several days. Chemokine induction was associated with a transient recruitment of neutrophils and monocytes to the brain, coupled with a sustained accumulation of macrophages, CD8+ T cells, NK cells and NKT cells. Strikingly, neutrophils, monocytes and T cells appeared to extravasate from the vasculature and/or CSF to infiltrate the brain parenchyma.

Conclusions

Prolonged exposure to a peripheral inflammatory stimulus triggers the recruitment of myeloid cells and lymphocytes to the brain. By altering the inflammatory or metabolic milieu of the brain, this novel method of immune-to-brain communication may have profound implications for patients with chronic inflammatory diseases, potentially leading to neuropsychiatric comorbidities.
Whole brain radiation therapy plus focal boost may be a suitable strategy for brain metastases in SCLC patients: a multi-center study
Authors: Ni Meng , Jiang Aijun , Liu Wenju , Sheng Yanxing , Zeng Haiyan , Liu Ning , Gao Qingxiao , Wang Yong , Yu Jinming , Yuan Shuanghu
Published: March 2020

Background

The treatment for brain metastases in small cell lung cancer (SCLC) is still controversial. The purpose of this study was to compare different brain radiotherapy treatments on SCLC patients with brain metastases.

Methods

In this multi-center retrospective study, SCLC patients who had undergone whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for brain metastases from January 2012 to December 2018 were retrospectively screened.

Results

A total of 263 eligible SCLC patients were included in this study, among whom, 73 were women and 190 were men. According to accepted brain radiotherapy, the remaining patients were divided into WBRT plus focal radiation boost (WBRT+boost), WBRT, and SRS groups. In pairwise comparisons of the overall survival (OS), WBRT+boost group led to longer survival than did WBRT both in all patients (17.9 vs 8.7 months; P < 0.001) and 140 matched patients (17.9 vs 11.7 months; P = 0.045). There were no significant differences in OS between WBRT+boost and SRS groups in all patients (17.9 vs 14.5 months; P = 0.432). Among 74 matched patients between WBRT+boost and SRS groups, however, patients who received WBRT+boost led to a longer survival than did SRS alone (21.8 vs 12.9 months; P = 0.040). In pairwise comparison of the intracranial progression-free survival time (iPFS), WBRT+boost group also showed survival advantages over WBRT (10.8 vs 6.5 months; P = 0.005) and SRS groups (10.8 vs 7.5 months; P = 0.032).

Conclusion

Due to the SCLC-derived multiple brain metastases and better survival time, focal radiation boost combined with adjuvant WBRT may be a preferred strategy for SCLC patients with brain metastases.