bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Novel Immunoassay With Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) for Therapeutic Drug Monitoring of Clozapine
Authors: Buckley Tiffany , Kitchen Christopher , Vyas Gopal , Siegfried Nathan A. , Tefera Eshetu , Chen Shuo , DiPaula Bethany A. , Kelly Deanna L.
Published: July 2020

Background:

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results.

Methods:

Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing.

Results:

The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21–159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690–0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979–0.997).

Conclusions:

The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.
Measuring Intracellular Concentrations of Calcineurin Inhibitors: Expert Consensus from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Expert Panel
Authors: Lemaitre Florian , Vethe Nils T. , D'Avolio Antonio , Tron Camille , Robertsen Ida , De Winter Brenda , Denicolo Amedeo , Koch Birgit C. P. , Venkataramanan Raman , Van Gelder Teun , Brunet Mercè , Bergan Stein , Hesselink Dennis A. , Wallemacq Pierre
Published: July 2020

Background:

Therapeutic drug monitoring (TDM) of the 2 calcineurin inhibitors (CNIs), tacrolimus (TAC) and cyclosporin A, has resulted in improvements in the management of patients who have undergone solid organ transplantation. As a result of TDM, acute rejection (AR) rates and treatment-related toxicities have been reduced. Irrespective, AR and toxicity still occur in patients who have undergone transplantation, showing blood CNI concentrations within the therapeutic range. Moreover, the AR rate is no longer decreasing. Hence, smarter TDM approaches are necessary. Because CNIs exert their action inside T lymphocytes, intracellular CNIs may be a promising candidate for improving therapeutic outcomes. The intracellular CNI concentration may be more directly related to the drug effect and has been favorably compared with the standard, whole-blood TDM for TAC in liver transplant recipients. However, measuring intracellular CNIs concentrations is not without pitfalls at both the preanalytical and analytical stages, and standardization seems essential in this area. To date, there are no guidelines for the TDM of intracellular CNI concentrations.

Methods:

Under the auspices of the International Association of TDM and Clinical Toxicology and its Immunosuppressive Drug committees, a group of leading investigators in this field have shared experiences and have presented preanalytical and analytical recommendations for measuring intracellular CNI concentrations.
Quantification of Serum Sulfamethoxazole and Trimethoprim by Ultra-fast Solid-Phase Extraction–Tandem Mass Spectrometry
Authors: Fatica Erica , Faber Jennifer , Gaffron Christopher , Bjergum Matthew , Langman Loralie , Jannetto Paul
Published: July 2020

Background:

The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used to treat a number of bacterial infections. TMP/SMX concentrations in serum are conventionally monitored using high-performance liquid chromatography (HPLC) or liquid chromatography tandem mass spectrometry. These methods require laborious manual extraction techniques and relatively long sample analysis times, necessitating the development of a simple, high-throughput method. A simple, high-throughput method to measure TMP/SMX using ultra-fast solid-phase extraction (SPE)–tandem mass spectrometry has been developed.

Methods:

Calibration standards, quality control materials, and patient samples were precipitated with acetonitrile containing isotopically labeled internal standards. Samples were vortexed, centrifuged for 5 minutes at 2053g, and the resulting supernatant was diluted in aqueous mobile phase and injected onto the C18 SPE cartridge. MS/MS analysis was performed by electrospray ionization in positive ion mode at a rate of <20 seconds per sample. A 5-point linear 1/x calibration curve was used to calculate sample concentrations.

Results:

The intra-assay precision coefficients of variation were <6% and <7% for SMX and TMP, respectively, and <10% for both interassay precision coefficients of variation. Comparison studies using 50 patient and spiked serum samples showed r2values of 0.9890 and 0.9853 andy-intercept values of −1.918 and −1.357, respectively compared with the HPLC reference method. All data points were <±15% of the mean. Linearity [r2= 0.9952 (SMX) and 0.9954 (TMP)] was established from 12 to 400 mcg/mL with a detection limit of 0.47 mcg/mL, and 1.2–40 mcg/mL with a detection limit of 0.06 mcg/mL, for SMX and TMP, respectively. For either drug, no significant carryover was observed after samples at the upper limit of quantification. No interference was observed from any of the 77 drugs and respective metabolites tested.

Conclusions:

A high-throughput SPE–tandem mass spectrometry method for TMP/SMX quantification was developed. The <20 seconds analysis time is a significant improvement compared with traditional HPLC and liquid chromatography tandem mass spectrometry methods, without sacrificing analytical performance.
Is Europe Facing an Emerging Opioid Crisis Comparable to the U.S.?
Authors: van Amsterdam Jan , Pierce Mimi , van den Brink Wim
Published: July 2020

In the U.S., an opioid overdose crisis has emerged, attributable to over-prescription of opioid analgesics, driven by aggressive marketing by pharmaceutical companies, followed by surging heroin overdose deaths, and more recently, by the high mortality rates predominately because of illicitly manufactured fentanyl and analogs of fentanyl. In Europe, the use of prescription opioids for pain management has also increased in the last 2 decades, although it is debatable as to whether this could lead to a similar opioid overdose crisis. To address this issue, recent trends in opioid prescription rates, prevalence rates of fatal and nonfatal incidents, and addiction care treatment were used as proxies of opioid-related harm. The current overview, comparing opioid use and its negative consequences in Germany, France, the U.K., and the Netherlands, using the same indicators as in the U.S., demonstrates that there is no evidence of a current or emerging opioid crisis in these European countries. Scotland, however, is an alarming exception, with high rates of opioid-related harms. Considering that the use of prescription opioids has been declining rather than increasing in Europe, an opioid crisis is not anticipated there yet. Authorities should, however, remain vigilant.
Coronary Disease in Pregnancy: Myocardial Infarction and Spontaneous Coronary Artery Dissection
Authors: CAMPBELL KATHERINE H. , TWEET MARYSIA S.
Published: July 2020

Pregnancy-related maternal mortality and morbidity rates continue to increase in the United States despite global improvements in maternal outcomes. The unique hemodynamic and physiological changes of pregnancy results in a 3- to 4-fold increased risk of acute myocardial infarction (AMI) which causes a substantial proportion of all maternal cardiac deaths. In addition to atherosclerosis, pregnancy-associated AMI is commonly caused by nonatherosclerotic etiologies such as spontaneous coronary artery dissection, embolus to the coronary artery, and coronary vasospasm. Herein, the epidemiology, etiologies, presentation, diagnosis, and management of AMI in pregnancy is discussed along with future directions for multidisciplinary care.
Clinical Presentation and Diagnosis of Polycystic Ovarian Syndrome
Authors: LENTSCHER JESSICA A. , DECHERNEY ALAN H.
Published: July 2020

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy with many clinical manifestations. The effects on women’s lives start at puberty and can last throughout her lifetime. Women frequently experience anovulatory menstrual cycles, infertility, hirsutism, obesity and increased risk of diabetes mellitus, hypertension, lipid abnormalities, and metabolic syndrome. PCOS is a heterogenous disorder, and a diagnosis of exclusion. In general, women afflicted will have menstrual irregularities, ultrasound findings of abnormal ovarian size and morphology, and clinical or laboratory evidence of hyperandrogenism. This chapter reviews the current understanding of PCOS, associated metabolic abnormalities, and diagnosis in reproductive-aged women, as well as adolescents.
FOVEAL AVASCULAR ZONE VOLUME
Authors: Xu Qiuzhuo , Zhang Weiwei , Zhu Hongjing , Chen Qiang
Published: July 2020

Purpose:

To propose a new clinical evaluation index, foveal avascular zone (FAZ) volume, and analyze its statistical significance.

Methods:

A semiautomatic method is proposed to measure the FAZ volume in optical coherence tomography angiography images as follows: The region of interest was flattened and annotated axially. The labeled pixels in the restored region of interest were counted as the FAZ volume. Linear regression and the independent samples t-test were performed for the statistical analysis.

Results:

Sixty-one normal, 64 high myopia, and 42 diabetic retinopathy eyes were imaged using optical coherence tomography angiography. For normal eyes, the FAZ volume correlates inversely with central macular thickness (superficial: P = 0.004; deep: P < 0.001) and positively with area (P < 0.001). For high myopia eyes, the deep plexus FAZ (P = 0.34) and total FAZ (P = 0.38) volumes show no significant difference, whereas the superficial plexus FAZ volume is significantly larger than control (P < 0.001). For diabetic retinopathy eyes, the superficial plexus FAZ (P = 0.001), deep plexus FAZ (P = 0.014), and total volumes (P = 0.002) are significantly larger than control.

Conclusion:

The FAZ volume is proposed for depicting the 3D structure of the FAZ. It shows greater sensitivity for vascular alteration that makes it meaningful for clinical analysis.
ASSESSMENT OF EARLY CHANGES IN SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY AFTER INITIATION OF TREATMENT WITH INTRAVITREAL AFLIBERCEPT (EYLEA) OVER A 12-WEEK PERIOD FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Korobelnik Jean-François , Souied Eric H. , Oubraham Hassiba , Razavi Sam , Mauget-Faÿsse Martine , Savel Helene , Chene Genevieve , Wolf Sebastian
Published: July 2020

Purpose:

To assess early changes in spectral-domain optical coherence tomography during the loading phase with intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration.

Methods:

In this prospective, open-label, single-arm, multicenter study, patients with neovascular age-related macular degeneration, who were antivascular endothelial growth factor treatment-naïve, received three monthly initial doses of intravitreal aflibercept 2 mg. The primary outcome was the proportion of patients with dry spectral-domain optical coherence tomography at 12 weeks, defined as an absence of intraretinal edema, intraretinal cysts, subretinal fluid, and subretinal pigment epithelium fluid.

Results:

Fifty eyes of 50 patients were investigated. At 12 weeks, 34.0% (17/50) had dry spectral-domain optical coherence tomography. Marked reductions were observed for all other spectral-domain optical coherence tomography parameters. The mean macular central thickness fell significantly from 463.2 ± 184.3 µm at baseline to 288.9 ± 76.8 µm at Week 12 (P < 0.0001). The mean best-corrected visual acuity also improved significantly from 61.0 ± 16.0 letters at baseline to 66.6 ± 19.0 letters at Week 12 (P = 0.0006).

Conclusion:

The anatomic and functional outcomes improved over the 12-week study period. All outcome variables peaked after the third aflibercept injection, confirming the benefit of three initial doses.
PATIENTS WEARING FACE MASKS DURING INTRAVITREAL INJECTIONS MAY BE AT A HIGHER RISK OF ENDOPHTHALMITIS
Authors: Hadayer Amir , Zahavi Alon , Livny Eitan , Gal-Or Orly , Gershoni Assaf , Mimouni Karin , Ehrlich Rita
Published: July 2020

Purpose:

To investigate the safety of face masks worn by patients during intravitreal injections.

Methods:

A prospective, qualitative, interventional study performed in a tertiary university hospital. Healthy volunteers were asked to wear three different professional surgical face masks while air leaks around the eyes were monitored. Three types of masks were investigated as follows: 1) surgical face mask with four tying strips, 2) surgical face mask with elastic ear loops and 3) 2200 N95 tuberculosis particulate face mask. For each session the periocular area was inspected for air leak during normal respiration, speech, and deep respiration. Detection of air leak was performed using the following two professional thermal cameras: FLIR A310—thermal camera and EyeCGas 2.0—super sensitive infrared camera used for detection of minute fugitive emissions of industrial gases.

Results:

Ten healthy volunteers were enrolled in this study. The experiment was repeated 45 times for each camera; 3 times for each of 3 mask types, on 5 volunteers, for a total of 90 trials. Air jets were detected originating from the superior edges of the masks radiating toward the eyes in 81% (73/90) of cases in total; 71% (32/45) with the FLIR camera and 91% (41/45) with the OPGAL camera. Air leaks were detected with all investigated mask types.

Conclusion:

Patients wearing face masks during intravitreal injections may be at a higher risk of endophthalmitis. Until further data are available, we recommend verifying proper face mask fitting and either taping the upper edges of the face masks with a medical adhesive tape or using an adhesive surgical drape around the injected eye.
Prevalence of chronic pain in opioid-maintained patients using the capture–recapture method: a nationwide population-based study
Authors: Delorme Jessica , Bertin Célian , Delage Noémie , Eschalier Alain , Ardid Denis , Authier Nicolas , Chenaf Chouki
Published: July 2020

Few studies all based on classical surveys have provided prevalence estimates of chronic pain (CP) in opioid-maintained patients (OMPs) but often had a limited patient sample size and a great variability in the prevalence estimates. This study sought to assess the prevalence of CP in the exhaustive population of OMPs using the capture–recapture method applied to the French nationwide health care database. Capture–recapture methods are increasingly used to estimate the prevalence of chronic conditions but have never been used in the specific context of CP in OMPs. Three large medical-administrative sources were used: the prescription drug database (A-list), the national hospital discharge database (M-list), and the pain center database (C-list). Between 2015 and 2016, 160,429 OMPs aged 15 years and older were identified and age- and sex-matched with 160,429 non-OMPs. All patients treated with analgesic drugs for ≥6 months (A-list) or diagnosed with CP (M- and C-list) were included. Capture–recapture analyses were performed to yield CP estimates with their 95% confidence intervals using log-linear models. In 2015 to 2016, 12,765 OMPs and 2938 non-OMPs with CP were captured. Most patients were male (67%) in OMPs and non-OMPs; median ages for OMPs and non-OMPs were 46 (interquartile range: 38-51) and 48 (41-53) years, respectively. The CP prevalence estimated in OMPs and non-OMPs ranged from 23.6% (14.9-46.2) to 32.1% (28.6-36.3) and from 7.28% (3.98-18.4) to 9.32% (7.42-12.1), respectively. This first study on CP in the exhaustive population of OMPs using the capture–recapture method demonstrated a high prevalence of CP in OMPs, 3- to 4-fold than in the general population.
Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity through netrin-1 in postoperative pain after orthopedic surgery for tibial fracture in mice
Authors: Cui Wei , Li Yize , Wang Zhen , Song Chengcheng , Yu Yonghao , Wang Guolin , Li Jing , Wang Chunyan , Zhang Linlin
Published: July 2020

Chronic postoperative pain hinders functional recovery after bone fracture and orthopedic surgery. Recently reported evidence indicates that caspase-6 is important in excitatory synaptic plasticity and pathological pain. Meanwhile, netrin-1 controls postsynaptic recruitment of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and synaptogenesis. The present work aimed to examine whether caspase-6 and netrin-1 contribute to fracture-induced postoperative allodynia. A mouse model of tibial fracture by intramedullary pinning was generated for inducing postoperative pain. Then, paw withdrawal threshold, spinal caspase-6 activity, netrin-1 secretion, AMPAR trafficking, and spine morphology were examined. Caspase-6 inhibition and netrin-1 knockdown by shRNA were performed to elucidate the pathogenetic mechanism of allodynia and its prevention. Whole-cell patch-clamp recording was performed to assess caspase-6's function in spinal AMPAR-induced current. Tibial fractures after orthopedic operation initiated persistent postsurgical mechanical and cold allodynia, accompanied by increased spinal active caspase-6, netrin-1 release, GluA1-containing AMPAR trafficking, spine density, and AMPAR-induced current in dorsal horn neurons. Caspase-6 inhibition reduced fracture-associated allodynia, netrin-1 secretion, and GluA1 trafficking. Netrin-1 deficiency impaired fracture-caused allodynia, postsynaptic GluA1 recruitment, and spine plasticity. The specific GluA2-lacking AMPAR antagonist NASPM also dose dependently prevented postoperative pain. The reduction of fracture-mediated postoperative excitatory synaptic AMPAR current in the dorsal horn by caspase-6 inhibition was compromised by recombinant netrin-1. Exogenous caspase-6 induced pain hypersensitivity, reversing by netrin-1 knockdown or coapplication of NASPM. Thus, spinal caspase-6 modulation of GluA1-containing AMPAR activation and spine morphology through netrin-1 secretion is important in the development of fracture-related postsurgical pain in the mouse.
Opioid-induced constipation in patients with cancer: a “real-world,” multicentre, observational study of diagnostic criteria and clinical features
Authors: Davies Andrew , Leach Charlotte , Butler Claire , Gregory Amanda , Henshaw Sarah , Minton Ollie , Shorthose Kate , Batsari Kabir M.
Published: July 2020

The aim of this study was to investigate opioid-induced constipation (OIC) in a large cohort of “real-world” patients with cancer; the objectives were to determine the prevalence of OIC, the utility of a simple screening question, the accuracy of the Rome IV diagnostic criteria, the clinical features of OIC (physical and psychological), and the impact of OIC (quality of life). One thousand patients with cancer were enrolled in the study, which involved completion of the Rome IV diagnostic criteria for OIC, the Bowel Function Index, the Patient Assessment of Constipation Quality of Life questionnaire, and the Memorial Symptom Assessment Scale—Short Form. Participants also underwent a thorough clinical assessment by an experienced clinician (ie, “gold-standard” assessment of OIC). Fifty-nine percent of patients were clinically assessed as having OIC, 2.5% as having another cause of constipation, and 19% as not having constipation but were taking regular laxatives. The simple screening question produced a number of false-negative results (19% of patients), whereas the Rome IV diagnostic criteria had an accuracy of 81.9%. Patients with OIC had more symptoms overall, higher Memorial Symptom Assessment Scale—Short Form subscale scores (and total score), and higher Patient Assessment of Constipation Quality of Life questionnaire subscale scores (and the overall score). Opioid-induced constipation was not associated with demographic factors, cancer diagnosis, performance status, or opioid equivalent dosage: OIC was associated with opioid analgesic, with patients receiving tramadol and transdermal buprenorphine having less constipation. The study confirms that OIC is common among patients with cancer pain and is associated with a spectrum of physical symptoms, a range of psychological symptoms, and an overall deterioration in the quality of life.
Molecular diagnostics for congenital heart disease: a narrative review of the current technologies and applications
Authors: Zu Bailing , Zheng Zhaojing , Fu Qihua
Published: July 2020

Congenital heart disease (CHD) is the most common birth defect worldwide. In recent years, the widespread application of innovative molecular diagnostic technologies in clinical scenarios has obviously increased the molecular diagnostic yields of CHD, providing evidence-based guidance for medical decision-making. These molecular diagnostic technologies include chromosome microarray analysis, targeted sequencing, exome sequencing, and genome sequencing. Furthermore, high-throughput sequencing technology has performed excellently in the clinical molecular diagnosis of CHD. This review provides an overview of the current technology and applications in the molecular diagnosis of CHD. The unmet issues and future directions in adapting novel genomic testing technologies to the molecular diagnosis of CHD in clinical settings are also addressed.
Is Sitagliptin Effective for Modulating Metabolic Disturbances Associated With Olanzapine in Schizophrenia Patients? A Double-blind Placebo-controlled Clinical Trial
Authors: Moghimi Sarani Ebrahim , Memari Elahe , Anushiravani Amir , Mowla Arash
Published: July 2020

Purpose/Background

The mortality rate of patients with schizophrenia due to metabolic disturbances is high. Our aim is to survey the effects of sitagliptin on metabolic disturbances associated with olanzapine in patients with schizophrenia.

Methods/Procedures

In this 12-week double-blind placebo-controlled clinical trial, 71 patients taking olanzapine (10 to 30 mg) for at least 1 month were randomly allocated to enter 1 of the 2 treatment groups (olanzapine plus placebo or olanzapine plus sitagliptin). Sitagliptin was added to patients ‘current medications with the dose of 100 mg/d. Physical examinations and measurement of anthropometric (body mass index and waist circumference) and laboratory parameters (fasting blood sugar, glycated hemoglobin, total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride) were measured at baseline, week 4, and week 12. The patients were assessed for any side effects of the medications in each visit.

Findings/Results

Sixty-one patients (30 in the sitagliptin and 31 in the placebo group) completed the trial. The anthropometric measurements at the end of the study did not differ between the 2 groups. glycated hemoglobin and total cholesterol were significantly lower in the sitagliptin group after 12 weeks. Other metabolic profile revealed either no change or minimal magnitude changes. No major side effect was reported.

Implications/Conclusions

Metabolic disturbances associated with olanzapine treatment in patients with schizophrenia can be modulated by sitagliptin.
Recurrence of Mania or Depression Among Adult Bipolar Patients Who Continued Using Lithium
Authors: Kishi Taro , Sakuma Kenji , Okuya Makoto , Matsuda Yuki , Esumi Satoru , Hashimoto Yasuhiko , Hatano Masakazu , Miyake Nobumi , Miura Itaru , Miyahara Kengo , Fujita Kiyoshi , Kawashima Kunihiro , Mishima Kazuo , Iwata Nakao
Published: July 2020

Background

The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown.

Methods

We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed.

Results

We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm.

Conclusions

The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-analysis were of short duration.
One-year change in resting heart rate and subsequent risk of hypertension in healthy Chinese adults
Authors: Li Hanlin , Dai Meng , Deng Zhihui , Peng Zhengliang , Huang Xingfu , Bai Yujia , Hou Lina , Ouyang Ping , Zhan Qiong , Zeng Qingchun , Xu Dingli
Published: July 2020

Background

Changes in baseline resting heart rate (RHR) appear to predict new-onset hypertension (NOH). However, RHR is a dynamic anthropometric parameter; thus, the association between changes in RHR and NOH requires further investigation.

Methods

We studied 10 403 participants who were initially normotensive and who had at least one routine health examination at baseline and 1 year later during 2011–2016. We compared the RHR between the baseline and 1-year follow-up. We defined hypertension as SBP ≥140 mmHg or DBP ≥90 mmHg. Participants were divided into three groups: RHR decreased, RHR unchanged [from 0 to 10 beats per minute (bpm)], and RHR increased ≥10 bpm. Cox regression analysis was performed to calculate relative risk with 95% confidence intervals (CIs) for the association between NOH and RHR change.

Results

During a mean follow-up period of 2.42 years, 1173 (11.28%) participants developed hypertension. After adjusting for age, sex, SBP, DBP, RHR and other confounders obtained at baseline, and compared with participants with unchanged RHR, participants with decreased RHR had a 17% decreased risk of NOH (adjusted hazard ratio: 0.83, 95% CI 0.73–0.95), whereas subjects with RHR that increased ≥10 bpm had a 23% increased risk of NOH (adjusted hazard ratio: 1.23, 95% CI 1.04–1.46).

Conclusion

A 1-year increase in RHR for initially normotensive subjects is an independent risk factor for subsequent hypertension.
Cardiac baroreflex function and vascular reactivity recovery after aerobic exercise in patients with early cirrhosis
Authors: Mira Pedro Augusto de C. , Henrique Diane M.N. , Loschi Renato Q. , Falci Maria F.A. , Guerrero Rosa V.D. , Machado Júnior Thompson B. , Barbosa Kátia V.B.D. , Ribeiro Tarsila C. da R. , Pace Fábio H. de L. , Martinez Daniel G. , Laterza Mateus C.
Published: July 2020

Objective

To investigate the effects of aerobic exercise on the cardiac baroreflex function and vascular reactivity in patients with cirrhosis.

Methods

Thirteen patients with cirrhosis were submitted to exercise and control intervention. At baseline and at 30 and 60 min following intervention, we evaluated cardiac baroreflex sensitivity (cBRS) and the baroreflex effectiveness index (BEI) using sequence technique. Vascular reactivity was assessed inducing reactive hyperemia before and 60 min after intervention.

Results

At baseline, there was no difference (P interaction = 0.848) between exercise (from 3.0 ± 0.34 to 14.60 ± 1.06 ml/100ml/min) and control sessions (from 2.38 ± 0.10 to 13.73 ± 1.05 ml/100ml/min) regarding the increase in forearm blood flow during reactive hyperemia. However, this response was higher postexercise (from 3.38 ± 0.31 to 16.58 ± 1.58 ml/100ml/min) than postcontrol intervention (from 2.04 ± 0.23 to 11.98 ± 1.16 ml/100ml/min, P interaction < 0.001). BEI increased at 30- and 60-min postexercise (from 32 ± 7 to 42 ± 7 and 46 ± 7%), but not after control intervention (from 33 ± 6 to 31 ± 5 and 33 ± 7%, P interaction = 0.014). In contrast, cBRS decreased at 30-min postexercise (from 10.3 ± 1.9 to 8.2 ± 1.4 and 10.3 ± 2.1 ms/mmHg) and increased postcontrol intervention (from 7.9 ± 0.9 to 10.5 ± 1.5 and 10.3 ± 1.3 ms/mmHg, P interaction = 0.012).

Conclusion

The results suggest that a single bout of aerobic exercise improved cardiac baroreflex function and increased vascular reactivity in patients with early-stage cirrhosis.
Burosumab in X-linked hypophosphatemia and perspective for chronic kidney disease
Authors: Balani Shanthi , Perwad Farzana
Published: July 2020

Purpose of review

Perturbations in phosphate and vitamin D homeostasis impacts skeletal health in children and adults. Study of inherited and acquired hypophosphatemic syndromes led to the discovery of fibroblast growth factor 23 (FGF23) as a potent regulator of phosphate and vitamin D metabolism, and advanced our understanding of the pathophysiology of mineral and bone disorder in chronic kidney disease (CKD-MBD). Here, we review a recently approved therapy for patients with X-linked hypophosphatemia (XLH) using a novel anti-FGF23 antibody, burosumab, and discuss the implications of such targeted therapy in CKD.

Recent findings

In children and adults with XLH, burosumab treatment significantly increased renal tubular phosphate reabsorption and normalized serum phosphorus concentrations. Prolonged treatment with burosumab showed a favorable safety profile, improved healing of rickets in children, and fractures and pseudofractures in adults. FGF23 excess in CKD is independently associated with left ventricular hypertrophy and cardiovascular mortality. Research strategies to lower FGF23 in animal models of CKD are rapidly advancing and a question that remains to be answered is whether FGF23 blockade will offer a new targeted intervention for disordered mineral metabolism in CKD.

Findings from recently concluded clinical trials in adults and children with XLH provide evidence for improved skeletal health with burosumab therapy with normalization of phosphate and vitamin D metabolism. Targeted anti-FGF23 antibody treatment of XLH has emerged as a novel therapeutic strategy to treat an inherited disorder of FGF23 excess.
Tubeless percutaneous nephrolithotomy: evaluation of minimal invasive exit strategies after percutaneous stone treatment
Authors: Veser Julian , Fajkovic Harun , Seitz Christian
Published: July 2020

Purpose of review

To provide an updated overview of different exit strategies for percutaneous nephrolithotomy (PCNL) in times of miniaturization and minimal invasive surgery.

Recent findings

The majority of the reported studies concluded that a tubeless procedure is associated with less patient discomfort and a shorter hospital stay compared to the standard PCNL. Additionally, no significant difference in the complication rate was observed, including postoperative fever, hematocrit decrease, stone-free rate, and urine extravasation.

Underlined by recent literature tubeless PCNL is a well tolerated and effective treatment. Nevertheless the decision whether or not to place a nephrostomy tube after PCNL is still depending on the clinical judgment and experience of the surgeon.
An up-to-date catalogue of urinary markers for the management of prostate cancer
Authors: Brönimann Stephan , Pradere Benjamin , Karakiewicz Pierre , Huebner Nicolai A. , Briganti Alberto , Shariat Shahrokh F.
Published: July 2020

Purpose of review

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Poor specificity and sensitivity of total PSA often results in over and sometimes underdetection/treatment. Therefore, more specific and sensitive biomarkers for the detection and monitoring especially of clinically significant PCa as well as treatment-specific markers are much sought after. In this field, urine has emerged as a promising noninvasive source of biomarkers.

Recent findings

RNA-based biomarkers are the most extensively studied type of urinary nucleic acids. ERG-Score/MiPS (Mi-Prostate Score) and SelectMDx might be considered as additional parameters together with clinical and imaging modalities to decrease unnecessary biopsies. miR Sentinel Tests could make it possible to accurately detect the presence of cancer and to distinguish low-grade from high-grade disease. In men with previous negative biopsies, PCA3 may suggest the need to repeat biopsy.

The definitive role of these markers and their clinical benefit needs future validation.
In-vitro protoscolicidal and immunomodulatory effects of Cinnamomum camphora and Ziziphora tenuior against Echinococcus granulosus protoscolices
Authors: Kanaan Manal H.G. , Anah Sadiya A. , Jasim Ghaith Ali , Ghasemian Abdolmajid
Published: July 2020

Objective:

Owing to side effects, drug resistance and recurrence of Echinococcus granulosus infestation following conventional therapies, seeking novel therapeutic approaches such as herbal medicines seems necessary. The aim of this study was assessment the antiparasitic and immunomodulatory effects of Cinnamomum camphora and Ziziphora tenuior herbal medicines against E. granulosus protoscolices.

Methods:

Various concentrations of extracts were prepared including 3, 5, 10, 25, 50 and 100 mg/ml. BALB/c mice liver samples were obtained from slaughter house and the protoscolices were taken under sterile conditions. Mouse CD11c + CD11c + dendritic cells were purified from other mononuclear cells and confirmed by flow cytometry.

Results:

C. camphora and Z. tenuior exhibited dose-dependent and time-dependent antiparasitic effects against E. granulosus protoscolices. Notably, the effect of C. camphora was higher than Z. tenuior. The 5 mg/ml of C. camphora and 25 mg/ml of Z. tenuior killed 100% of protoscolices during 10 min. Extracts had insignificant macrophage cytotoxicity in MTT assay. Z. tenuior at 10 and 50 mg/ml decreased CD86 (P = 0.212) and MHC II (P = 0.0711) markers, but increased CD40 (P = 0.181) and at 100 mg/ml increased CD40 (P = 0.002), CD86 (P = 0.091) and MHC II (P = 0.113). Furthermore, C. camphora at 10 and 50 mg/ml increased CD40 (P = 0.0311) and MHC II (P = 0.0184) significantly. At these concentrations, decreased CD86 nonsignificantly, but at 100 mg/ml decreased all markers significantly (P < 0.05).

Conclusion:

C. camphora and Z. tenuior herbal medicines exerted substantial antiparasitic effects against hydatid cyst protoscolices. Future formulations of these herbal medicines will be promising because of low side effects and potential effects.
Pathogenic bacteria of diabetic-associated infections and their pathogenesis
Authors: Khazaal Saba S. , Talha Mustafa H. , Raheem Anmar A.
Published: July 2020

The diabetic patients have tendencies to develop infections in presence of hyperglycemia makes mucosal epithelial more susceptible to infections. Diabetic mellitus causes a sever deregulation of immune response in a healthy human body. The suppressed production of immune pepetides and altered immune, susceptibility to infections are much higher in immunosuppressed patients with diabetes mellitus. The human host and microorganisms normally exist in a balanced relationship. Infection occurs when pathogens are able to resist host's immune system and subsequently invade systemic host responses. The reasons why infections do not recover are related to local factors associated with the infections and also with comorbidities such as diabetes. In this review, we discuss the influence of diabetes in bacterial infection and their mechanism emphasizing their role in bacterial pathogensis.
Adolescents’ Awareness of and Attitudes Toward Expedited Partner Therapy Provided in the Emergency Department
Authors: Pickett Michelle L. , Hoehn Erin F. , Visotcky Alexis M. , Norman Brandy , Drendel Amy L.
Published: July 2020

Background

Adolescents and young adults account for half of the 20 million new cases of sexually transmitted infections each year. Expedited partner therapy (EPT) has been shown to decrease reinfection rates and is recommended by the Centers for Disease Control and Prevention. We aimed to (1) assess adolescents’ awareness of EPT, (2) assess their likelihood of giving EPT received in the pediatric emergency department (PED) to their partner(s), and (3) identify factors associated with increased likelihood of giving EPT to their partner(s).

Methods

Adolescents and young adults aged 14 to 22 years seeking care in 2 PEDs participated in a survey. Main outcomes were EPT awareness and likelihood of giving EPT to his/her partner(s). Patients were dichotomized into likely and not likely to provide partner(s) with EPT based on answers to a 5-point Likert scale question. χ2 and t tests were used to analyze the data.

Results

Three hundred ninety-three participants were included. Only 11% (n = 42) were aware of EPT; however, 80% (n = 316) reported to be likely to give EPT received in the PED to his/her partner(s). Study site, being sexually active, and engaging in high-risk sexual behaviors were associated with an increased likelihood of giving EPT to their partner(s) (P < 0.05).

Conclusions

Many adolescents are not aware of EPT; however, most were theoretically likely to give EPT received in the PED to his/her partner(s). With increasing rates of sexually transmitted infections and high utilization of the PED for adolescent reproductive health services, efforts to incorporate the use of EPT in PED workflows would be beneficial.
Rehabilitation Therapy for a COVID-19 Patient Who Received Mechanical Ventilation in Japan
Authors: Saeki Takuya , Ogawa Fumihiro , Chiba Ryosuke , Nonogaki Manabu , Uesugi Jo , Takeuchi Ichiro , Nakamura Takeshi
Published: July 2020

A 65-yr-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1), he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19, and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.
Pricing and Paying for Cancer Drugs
Authors: Hyman David A. , Silver Charles
Published: July 2020

The US system for pricing and paying for cancer drugs is badly broken. The evidence is all around us—whether we focus on total spending, the breathtakingly high prices for chimeric antigen receptor T-cell therapy, the exceedingly high prices for many recently introduced drugs that offer only marginal improvements over existing treatments, or the increasing unaffordability of patient copayments. These problems are compounded by the distortions created by our payment policies, which do not take account of the value of competing treatment options and are structured in ways that distort physicians' incentives. We review the key drivers of cancer drug spending and consider the trade-offs of various policy options for addressing this problem.
Relationship Between Work Experience and Safety Climate in Veterans Affairs Nursing Homes Nationwide
Authors: Quach Emma D. , Kazis Lewis E. , Zhao Shibei , McDannold Sarah E. , Clark Valerie A. , Hartmann Christine W.
Published: July 2020

Objectives

Staff values and beliefs about resident safety (safety climate) represent one potential driver of nursing home safety. Staff with more work experience (length of service) may possess richer knowledge of resident safety for strengthening safety climate. We investigated the association of length of service with safety climate in the U.S. Department of Veterans Affairs nursing homes or Community Living Centers (CLCs).

Methods

Fifty-six of 134 CLCs participated in 2017 and then 2018 in the previously validated CLC Employee Survey of Attitudes about Resident Safety, which comprised 7 safety climate domains and employee characteristics. We conducted 2 cross-sectional analyses of length of service on each safety climate domain, controlling for occupation, shift, work hours, and clustering by VA hospital, service network, and geographic region, in mixed random-effect regression models.

Results

A total of 1397 and 1645 staff participated in the survey (26% and 28% response rates) at round 1 and 2, respectively. At each round participants working greater than 6 months were less positive than those working less than 6 months about supervisor commitment to safety, coworker interactions around safety, and CLC global ratings.

Conclusions

Differences in work experience contributed to incongruence in perceptions about supervisors, coworkers, and the facility. Workers with more experience may have higher perceived job aptitude and thus higher expectations of supervisory recognition and more criticisms of coworkers. Pairing experienced workers with newer ones may narrow the knowledge gap and increase collaboration. Huddles, team meetings, and organizational initiatives represent opportunities to recognize and leverage experienced workers’ accumulated safety knowledge.
Cost-effectiveness of integrated HIV prevention and family planning services for Zambian couples
Authors: Wall Kristin M. , Kilembe William , Inambao Mubiana , Hoagland Alexandra , Sharkey Tyronza , Malama Kalonde , Vwalika Bellington , Parker Rachel , Sarkar Supriya , Hunter Ken , Streeb Gordon , Mazarire Christine , Tichacek Amanda , Allen Susan
Published: July 2020

Objective:

To present the incremental cost from the payer's perspective and effectiveness of couples’ family planning counseling (CFPC) with long-acting reversible contraception (LARC) access integrated with couples’ voluntary HIV counseling and testing (CVCT) in Zambia. This integrated program is evaluated incremental to existing individual HIV counseling and testing and family planning services.

Design:

Implementation and modelling.

Setting:

Fifty-five government health facilities in Zambia.

Subjects:

Patients in government health facilities.

Intervention:

Community health workers and personnel promoted and delivered integrated CVCT+CFPC from March 2013 to September 2015.

Main outcome measures:

We report financial costs of actual expenditures during integrated program implementation and outcomes of CVCT+CFPC uptake and LARC uptake. We model primary outcomes of cost-per-: adult HIV infections averted by CVCT, unintended pregnancies averted by LARC, couple-years of protection against unintended pregnancy by LARC, and perinatal HIV infections averted by LARC. Costs and outcomes were discounted at 3% per year.

Results:

Integrated program costs were $3 582 186 (2015 USD), 82 231 couples received CVCT+CFPC, and 56 409 women received LARC insertions. The program averted an estimated 7165 adult HIV infections at $384 per adult HIV infection averted over a 5-year time horizon. The program also averted 62 265 unintended pregnancies and was cost-saving for measures of cost-per-unintended pregnancy averted, cost-per-couple-year of protection against unintended pregnancy, and cost-per-perinatal HIV infection averted assuming 3 years of LARC use.

Conclusion:

Our intervention was cost-savings for CFPC outcomes and CVCT was effective and affordable in Zambia. Integrated couples-focused HIV and family planning was feasible, affordable, and leveraged HIV and unintended pregnancy prevention.
Exploring patterns and predictors of suicidal ideation among pregnant and postpartum women living with HIV in Kilimanjaro, Tanzania
Authors: Knettel Brandon A. , Mwamba Rimel N. , Minja Linda , Goldston David B. , Boshe Judith , Watt Melissa H.
Published: July 2020

Objective:

Pregnant and postpartum women living with HIV face disproportionate risk of depression and suicide, particularly in low-income and middle-income countries. This study examined patterns and predictors of suicidal ideation among women living with HIV in antenatal care in Kilimanjaro, Tanzania.

Design:

We conducted a longitudinal cohort study of 200 pregnant women living with HIV, with surveys conducted during pregnancy and 6 months postpartum.

Methods:

Pregnant women were recruited during HIV and antenatal care visits at nine clinics. A structured questionnaire was verbally administered in Kiswahili by a trained study nurse. We used simple frequencies and t-tests to measure patterns of suicidal ideation and logistic regression to assess factors associated with suicidal ideation.

Results:

Suicidal ideation was endorsed by 12.8% of women during pregnancy and decreased significantly to 3.9% by 6 months postpartum. Ideation was not significantly greater among participants newly diagnosed with HIV. In univariable analyses, suicidal ideation was associated with depression, anxiety, HIV stigma, single relationship status, unknown HIV status of the father of the baby, negative attitudes about antiretroviral medication, and low social support. In the multivariable model, women experiencing anxiety and HIV stigma were significantly more likely to endorse suicidal ideation during pregnancy.

Conclusion:

Suicidal ideation and associated feelings of hopelessness are a critical challenge in antenatal care among women living with HIV, with important implications for quality of life, care engagement, and survival. To better support patients, targeted approaches to address anxiety, depression, stigma, and hopelessness must be prioritized, including crisis support for suicide prevention.