Clinical Practice Protocols Research Articles

Bedside testing for precision pain medicine.

In recent years, the identification of therapy responders has become an increasing focus of pain research. On the basis of laboratory quantitative sensory testing, subgroups of patients were identified, which have been shown to predict treatment response. However, the high cost and time expenditure limits the use of these lab-QST protocols in clinical practice and large clinical trials. Recently, different bedside testing protocols were developed as easy-to-use alternative for lab-QST. In addition, patients can be subgrouped based on their symptoms by use of patient-reported outcome measures. First results suggest that these approaches can be used to stratify patients into pathophysiological-plausible subgroups predictive for treatment response. This review presents recently developed bedside approaches that can be implemented as stratification tools in future clinical trials to realize individualized pain medicine. Being complementary rather than replaceable, future studies should combine questionnaires and sensory testing and apply them prospectively in large clinical trials.

Enablers and barriers in hospital-to-home transitional care for stroke survivors and caregivers: A systematic review.

To synthesise qualitative research evidence on the experience of stroke survivors and informal caregivers in hospital-to-home transitional care. Due to a shortened hospital stay, stroke survivors/caregivers must take over complex care on discharge from hospital to home. Gaps in the literature warrant a meta-synthesis of qualitative studies on perceived enablers and barriers during this crucial period. A systematic review and meta-synthesis. A review was guided by Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist where six databases were searched from April to June 2020 including CINAHL Plus, MEDLINE, PsycINFO, Scopus, Web of Science and ProQuest and ProQuest Dissertations and Theses. There was no date limit to the search. Selected studies were critically appraised. A thematic synthesis approach was applied. The synthesis of 29 studies identified three major findings. First, partnerships with stroke survivors/caregivers empower discharge preparation, foster competence to navigate health and social care systems and activate self-management capabilities. Second, gaps in discharge planning and the lack of timely postdischarge support contribute to unmet care needs for stroke survivors/caregivers and affect their ability to cope with poststroke changes. Third, stroke survivors/caregivers expect integrated transitional care that promotes shared decision-making and enables long-term self-management at home. Hospital-to-home transition is a challenging period in the trajectory of poststroke rehabilitation and recovery. Further research is required to deepen understandings of all stakeholders' views and address unmet needs during transitional care. Protocols and clinical guidelines relating to discharge planning and transitional care need to be reviewed to ensure partnership approach with survivors/caregivers in the design and delivery of individualised transitional care. Stroke nurses are in a unique position to lead timely support for survivors/caregivers and to bridge service gaps in hospital-to-home transitional care.

Implementing a new antibiotic allergy protocol in clinical practice: well-trusted but not used.

BackgroundSuboptimal antibiotic prescriptions in patients with an antibiotic allergy label lead to increased incidence of adverse events and antimicrobial resistance (AMR). An antibiotic allergy protocol was developed in a Dutch academic hospital guiding optimal and safe antibiotic use in potentially penicillin-allergic patients. Informed by previous studies of implementation processes in clinical care, we studied the implementation of this protocol.MethodsMedical professionals in the Departments of Surgery, Internal Medicine, and Pulmonary Care were interviewed. Additionally, focus groups were conducted in Internal Medicine and Pulmonary Care to validate the outcomes of the interviews.ResultsDissemination of the protocol via the regular online hospital-wide guidance system did not have a significant impact on the knowledge about or use of the protocol. If healthcare professionals found the protocol, they thought it was valuable and expressed trust in the expertise embodied in it. However, its use in practice was rather minimal. Interviewees doubted the accuracy of the patient’s histories about their previous adverse drug reactions, and/or the information in their medical records and concluded that adherence to the expert guideline was needlessly risky. They felt the acute allergic reaction risk for a patient outweighed the risk of suboptimal therapy or future AMR.ConclusionsFor successful implementation and dissemination of the protocol, the accessibility of the protocol, the information about the actual risks of following the protocol and the registration of allergic history should be improved. However, whether this actually results in improvement also depends on changes in the hospital culture and organization.

Impact of the Implementation of a Vancomycin Protocol on Trough Serum Vancomycin Concentrations in a Pediatric Intensive Care Unit.

Vancomycin is an antibiotic that is widely used in pediatric intensive care, but the safe and effective use of this drug is challenging. This study aimed to assess the impact of a vancomycin protocol on trough serum concentrations. We conducted a retrospective quasiexperimental study in patients aged ≤18 years in intensive care who received vancomycin for at least 5 days. Patients were divided into two groups: before and after a protocol implemented in 2017 that suggested an initial vancomycin dose of 60 mg/kg/day, target serum levels of 15-20 μg/mL, and dose adjustments. We compared patient characteristics, target serum level achievement, and vancomycin levels over time. Each group contained 65 patients; most were male infants with heart disease as the main reason for hospitalization. Only 29.2% of the patients had pretreatment cultures for bacteria identification recorded, with 1.5% identified as methicillin-resistant Staphylococcus aureus. For the first serum levels, 10.8% of patients in the pre-protocol group and 21.5% in the post-protocol group achieved the 15-20 μg/mL target (p = 0.153); during the first 5 days of treatment, this proportion significantly increased from 52.3 to 73.8% (p = 0.018). We observed a difference between the first and fifth levels: 8.9 μg/mL (95% confidence interval [CI] -3.1 to 21) pre-protocol and 0.4 μg/mL (95% CI -6.1 to 6.9) post-protocol (p = 0.175). Reaching adequate trough vancomycin concentrations in critically ill pediatric patients remains a challenge, and clinical practice protocols allow better dose adjustment and control even when monitoring technologies are unavailable.

Clinical practice competencies and associated factors among graduating nursing students attending at universities in Northern Ethiopia: institution-based cross-sectional study

ObjectiveTo assess clinical practice competencies and associated factors among graduating nursing students attending public universities found in the Amhara Region, EthiopiaDesignInstitution-based cross-sectional study designSettingThe study was conducted in six universities...

PROPOSAL OF A UNIVERSAL OFFICE BLOOD PRESSURE MEASUREMENT PROCEDURE FOR CLINICAL AND SCIENTIFIC USE

Objective: Office blood pressure measurement (OBPM) procedures recommended in guidelines and applied in studies vary highly. The current European Societies of Cardiology/Hypertension (ESC/ESH) guidelines for OBPM are impractical to use in clinical settings and trials and lack scientific evidence. Our aim was to explore the meaning of the fourth BP measurement as recommended by ESC/ESH and to study whether a simplified OBPM procedure is feasible without loss of quality. Design and method: Four sequentially taken blood pressure measurements (BPMs) were used to calculate blood pressure (BP) as a mean of the second/third systolic/diastolic BPM (S2S3/D2D3), or as a mean of the third/fourth BPM (S3S4/D3D4). Patients were stratified according to the absolute difference between the first/second BPM (S1S2/D1D2) into >10 mmHg and < =10 mmHg. A linear model was used to predict S3S4/D3D4 from S2S3/D2D3. Results: Complete measurements were available in 802 patients. 206 patients (25.7%) had an absolute S1S2 difference >10 mmHg, 60 patients (7.5%) for D1D2. Correlation tests showed a median decrease from S2S3 to S3S4 of 0.5 mmHg and 0.5 mmHg for D2D3 to D3D4 (p < 0.0005 for both). For patients with S1S2 >10 mmHg the median decrease was 0.0 mmHg (p = 0.174), with S1S2 < = 10 mmHg 0.5 mmHg (p < 0.0005), with D1D2 >10 mmHg 1.0 mmHg (p = 0.269), with D1D2 <=10 mmHg 0.5 mmHg (p < 0.0005). There was a linear relationship between S2S3/S3S4 (R2 = 0.944, p < 0.0005, Figure(A); for patients with S1S2 >10 mmHg R2 = 0.958, p < 0.0005, Figure(B), with < =10 mmHg R2 = 0.953, p < 0.0005, Figure(C)) and D2D3/D3D4 (R2 = 0.911, p < 0.0005, Figure(D); for patients with D1D2 >10 mmHg R2 = 0.694, p < 0.0005, Figure(E), with < = 10 mmHg R2 = 0.968, p < 0.0005, Figure(F)). S3S4 and D3D4 could be predicted with an accuracy of 0.967/0.960 from S2S3 and D2D3. Conclusions: A fourth BPM does not provide any significant benefit in the context of a standardized OBPM procedure. Therefore, we propose a simplified procedure based on the mean of the second/third standardized OBPM measurement and refrain from a fourth measurement in both clinical practice and study protocols.

Administration of 3% Sodium Chloride Through Peripheral Intravenous Access: Development and Implementation of a Protocol for Clinical Practice.

Patients with traumatic brain injury, cerebral edema, and severe hyponatremia require rapid augmentation of serum sodium levels. Three percent sodium chloride is commonly used to normalize or augment serum sodium level, yet there are limited data available concerning the most appropriate route of administration. Traditionally, 3% sodium chloride is administered through a central venous catheter (CVC) due to the attributed theoretical risk of phlebitis and extravasation injuries when hyperosmolar solution is administered peripherally. CVCs are associated with numerous complications, including arterial puncture, pneumothorax, infection, thrombosis, and air embolus. Peripherally infused 3% sodium chloride may bypass these concerns. To explore the evidence for peripherally infused 3% sodium chloride and to implement the findings. The Iowa Model of Evidence-Based Practice (EBP) was used to guide the project. A multidisciplinary team was established, and they developed an evidence-based protocol for the administration of 3% sodium chloride using peripheral intravenous catheters (PIVs), identified potential barriers to implementation, and developed targeted education to implement this practice change in a large academic medical center. Of the 103 patients in this project, only three (2.9%) identified adverse events. Two were associated with continuous infusions, and one was associated with a bolus infusion. This is the first study to describe a multidisciplinary protocol development and implementation process for the administration of 3% sodium chloride peripherally. Utilizing a multidisciplinary team is critical to the success of an EBP project. Implementing an evidence-based PIV protocol with stringent monitoring criteria for the administration of 3% sodium chloride has the potential to reduce adverse events related to CVC injury.

Options for Veterans Experiencing Sleep Impairment

This article provides an overview of methods to evaluate and manage sleep disorders in veterans, in particular, chronic insomnia. Treatment of sleep disorders may present a challenge for nurse practitioners (NPs) caring for veterans. Evidence-based guidance for pharmacotherapy, psychotherapy and some alternative and complementary modalities have shown efficacy in managing sleep disorders. It is suggested NPs consider utilize the Department of Veteran Affairs patient-centered care clinical practice protocols with consideration of a patient-centered approach when evaluating patients and determining modalities for treatment of sleep disorders.

An observational study «FOLLITROPIN» comparing the efficacy of follitropin alpha biosimilar: the real-world data

Introduction. The efficacy and safety of biosimilar follitropin alpha have been demonstrated in randomized blinded prospective clinical trials of phases I and III. Unfortunately, there is a gap between the clinical trials and real clinical practice data. The real-world patient data helps to create an evidence-based background for successful implementation of medicine at everyday practice in a nonselected population.Aim: to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.Materials and Methods. A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.Results. The overall clinical efficacy of ovarian stimulation cycles (N = 5484) was: oocytes retrieved - 9.5 ± 7.2, mature (MII) - 6.8 ± 6.6, fertilized (2PN) - 6.1 ± 5.8, clinical pregnancy per ET (PR) - 38.4 %. Mixed gonadotropin protocols (N = 2625) vs. monotherapy with Primapur® (N = 2859): oocytes retrieved - 8.6 ± 6.8 vs. 10.3 ± 7.4 (p < 0.001), mature (MII) - 6.7 ± 6.2 vs. 7.7 ± 6.9 (p < 0.001), fertilized (2PN) - 5.8 ± 5.2 vs. 7.2 ± 6.2 (p < 0.001). There were statistically significant differences between oocyte yields in mixed vs. monotherapy protocols due to subgroup differences, including age, body mass index (BMI) and IVF/ICSI attempts. No statistically significant differences were found for PR: 39.3 % vs. 37.6 % (p = 0.314). Monotherapy protocols with GnRH antagonist OS (N = 2183) vs. GnRH agonist (N = 676) revealed: oocytes retrieved - 10.5 ± 7.5 vs. 9.6 ± 7.0 (p = 0.032), mature (MII) - 7.6 ± 6.9 vs. 6.7 ± 5.7 (p < 0.001), fertilized (2PN) - 7.3 ± 6.3 vs. 5.7 ± 5.0 (p < 0.001). There were statistically significant differences between BMI and IVF/ICSI attempts. No statistically significant differences were found for PR: 37.9 % vs. 35.9 % (p = 0.482). All medicines were well tolerated and no serious adverse reactions were reported.Conclusion. This was the largest retrospective observational study conducted in the field of fertility in Russia and involved 5484 ovarian stimulation protocols at 35 IVF clinics. The obtained results demonstrated similar clinical efficacy for follitropin alpha biosimilar Primapur® in different OS protocols in real clinical practice.

A national collaborative to spread and scale paramedics providing palliative care in Canada: Breaking down silos is essential to success

A national collaborative has been launched in Canada to spread and scale up the Paramedics Providing Palliative Care model. This builds on the knowledge that paramedics in the 9-1-1 (emergency/unscheduled) and scheduled models of care are both historically and currently asked by the public to provide urgent symptom relief within the context of a palliative approach, and that approximately 40% of dying people visit the emergency department in the last two weeks of life despite 70% wishing to die at home. A model of care including a palliative care clinical practice guideline or protocol, specific training, and a mechanism for sharing of goals of care, has been proven to improve the palliative and end of life experience for patients with palliative care needs and their families. It increases the comfort and confidence of paramedics and has benefits to the broader health system. Meaningful and very broad stakeholder engagement and inter-sectoral collaboration is absolutely essential to the success of this innovative approach to care.

Practice and outcomes of airway management in patients with cervical orthoses

Increasing evidence indicates an association of video laryngoscopy with the success rate of airway management in patients with neck immobilization. Nevertheless, clinical practice protocols for tracheal intubation in patients immobilized using various types of cervical orthoses and the outcomes remain unclear. We retrospectively assessed the tracheal intubation techniques selected for patients immobilized using cervical orthoses from 2015 to 2018. The endpoints were the intubation outcomes of the different techniques and the factors associated with the selection of the technique. We included 218 patients, 118 of whom wore halo vest braces (halo vest group) and 100 wore cervical collars (collar group). GlideScope video laryngoscopy (GVL) and fiberoptic bronchoscopy (FOB) were the initial intubation methods in 98 and 120 patients, respectively. GVL had a higher first-attempt success rate than did FOB in the collar group (p=0.002) but not in the halo vest group (p=0.522). GVL was associated with a lower risk of episodes of SaO2< 90% (adjusted relative risk [aRR], 0.11; 95% CI, 0.02-0.67; p=0.016) and shorter intubation time (aRR, -3.52; 95% CI, -4.79∼-2.25; p<0.001) in the collar group. However, in the halo vest group, more frequent requirement of a rescue technique (p=0.002) and necessity of patient awakening (p=0.001) was noted when GVL was used. Use of the halo vest brace and noting of severe cord compression were independent predictors of the initial selection of FOB. Caution should be exercised when using GVL for tracheal intubation in patients immobilized using halo vest braces.

Evaluation of image quality and patient exposure in fluoroscopy using a phantom: Is there any clinical relevance?

ObjectiveTo investigate the impact of X-ray preset acquisition protocol settings on fluoroscopy image quality (IQ) and radiation exposure. Materials & MethodsA quality control (QC) phantom was imaged with a modern digital C-arm system, using various preset fluoroscopy protocols. IQ was assessed using human observers and in-house software for automated evaluation, based on contrast-to-noise ratios of details and their background. Patient radiation exposure was evaluated using the displayed Incident Air-Kerma and Kerma-Area Product values. ResultsProtocol selection affects radiation exposure by a factor of about 3. IQ evaluation showed that acquisition protocols produce images with quite different characteristics. The visual IQ evaluation method was time consuming and cumbersome. The automated method, utilized the visual IQ evaluation results for calibration of detection thresholds. However, it failed to reproduce these results for all images and details types. In some images, digital image processing created artifacts which affected the pixel value distributions around details in a way that could be handled only by the human vision. ConclusionManufacturers provide many preset protocols designated for specific clinical uses, which have large impact on IQ characteristics and radiation exposure. However, protocol settings’ selection rationale is essentially a “black box” for the end user. Though QC phantoms are currently used for IQ evaluation, they are not appropriate for drawing firm conclusions concerning the expected performance of each protocol in clinical practice. Currently, there is no consensus on the optimum technical characteristics of preset protocols for specific procedures. More work is needed in this area.

The management of pain, delirium and dyspnea at home: a proposal for management algorithms

. The management of pain delirium and dyspnea at home: a proposal for management algorithms. The project "E-health, advanced nursing care for the cancer patient at home" includes the implementation of an app (and the evaluation of the feasibility of its use) but the core aspect is the availability of a group of nurses able to prevent and answer the needs of the palliative care patients. The three pillars of the project are: training, organisation and the provision of instruments able to offer a guide to nurses when at home of the patients or when called in case of problems. In this issue 2 of the clinical practice protocols for the management of pain, delirium and dyspnea are presented. Each protocol is the result of a constant dialogue between the medical and nursing staff of the Palliative Care and Oncology units. The algorithms can be used by nurses to orient the patient in the choice of the most appropriate at need drugs.

Effect of position and exercise on measurement of muscle quantity and quality: towards a standardised pragmatic protocol for clinical practice

BackgroundUltrasonography is an emerging non-invasive bedside tool for muscle quantity/quality assessment; Bioelectrical Impedance Analysis (BIA) is an alternative non-invasive bedside measure of body composition, recommended for evaluation of sarcopenia in clinical practice. We set out to assess impact of position and exercise upon measures towards protocol standardisation.MethodsHealthy volunteers aged 18–35 were recruited. Bilateral Anterior Thigh Thickness (BATT; rectus femoris and vastus intermedius), BATT: Subcutaneous Ratio (BATT:SCR), and rectus femoris echogenicity were measured using ultrasound and BIA was performed; 1) lying with upper body at 45° (Reclined), 2) lying fully supine at 180o (Supine), 3) sat in a chair with upper body at 90o (Sitting), and 4) after exercise Reclined. Variability of Skeletal Muscle Mass (SMM) by two different equations from BIA (SMM-Janssen, SMM-Sergi), phase angle, fat percentage, and total body (TBW), extracellular (ECW), and intracellular water (ICW) were assessed.ResultsForty-four participants (52% female; mean 25.7 years-old (SD 5.0)) were recruited. BATT increased from Reclined to Sitting (+ 1.45 cm, 1.27–1.63), and after exercise (+ 0.51, 0.29–0.73). Echogenicity reduced from Reclined to Sitting (− 2.1, − 3.9 – -0.26). SMM-Sergi declined from Reclined to Supine (− 0.65 kg, − 1.08 – − 0.23) and after exercise (− 0.70 kg, − 1.27 – -0.14). ECW increased from Reclined to Sitting (+ 1.19 L, 0.04–2.35). There were no other statistically significant changes.ConclusionStandardisation of protocols is especially important for assessment of muscle quantity by ultrasonography; BIA measurements may also vary dependent on the equations used. Where possible, participants should be rested prior to muscle ultrasonography and BIA, and flexion of the knees should be avoided.

Mechanical standardisation of mammographic compression using Volpara software

IntroductionAlthough breast compression is required in routine mammographic practices, current subjective protocols enforcing ‘breast tautness’ have minimal clinical reproducibility. Whilst objective guidelines of target force (daN) do not consider breast volumes, new measures of pressure (kPa) account for associated variations. The study aims to determine characteristic compressive forces applied at an Australian diagnostic breast clinic, thereby establishing performance success in achieving ideal pressures of 10 kPa. MethodsParameters of 1972 mammograms were analysed retrospectively from a South Australian diagnostic breast clinic. Raw data were processed using VolparaDensity software; applied compression (force/pressure), breast thickness, breast volume, breast density and average glandular dose estimates were investigated based on breast/paddle contact areas. ResultsDistributions of applied average forces is large, yet distributions of applied average pressures are larger; this is internationally comparable. Regarding force-compressions, 98.6% are >5 daN, 16.6% are >10 daN, and 0.0% are >15 daN. Regarding pressure-compressions, 94.5% are >5 kPa, 36.0% are >10 kPa, and 6.3% are >15 kPa. Measures of average breast thickness, volume and density show anatomically consistent trends, with average glandular dose values constant, albeit high. ConclusionsThere was a high level of variation of applied compression forces in relation to breast/paddle contact area and an even higher variation in applied pressure. This is comparable with existing literature. Real-time compression pressure standardisation may benefit examination consistency. The relationship between breast volume, contact area, compression force and resultant compression pressure may aid in developing an objective compression protocol for clinical practice. Implications for practicePractical guidelines may increase the reproducibility of image acquisition, whilst optimizing patient discomfort and additional radiation dose from image repeats. Patient compliance may increase in accordance with perceived advantages of mechanical standardisation, ultimately aiding in the detection of early-stage breast cancer.

Management of dental office during COVID-19 Pandemic

Novel Coronavirus (COVID-19) is a deadly protein molecule devastating the humankind and has brought down the life to a standstill. Its effect is determined by the interaction among the agent, the host and the environment. The proven fact that the spread of COVID-19 is air-borne has made it mandatory for the dental fraternity to follow a systematic protocol in clinical practice. A proper history of travel and exposure, thermal scanning, symptoms of sore throat, dry cough and difficulty in breathing makes you suspect an individual with COVID-19. It is imperative to consider only emergency and essential dental procedures to be carried out under strict aseptic measures, not only for suspects but also for routine patients. COVID-19 and dentistry are very closely related to each other as dental professionals are directly working in the oral cavity. Although the Ministry of Health & Family Welfare has issued comprehensive guidance to prevent the occurrence of hospital-acquired infection (HAI) in health facilities, the practice of universal precautions might still be lacking in many dental professionals due to improper knowledge. Data acquisition was carried out using the keywords, COVID-19, control of infection, and patient management in dental offices in PubMed, Medline, ProQuest, etc., electronic databases. There was also a manual scan of many journals and books, and highly relevant papers were considered for the present study.

Echocardiographic screening for the anomalous aortic origin of coronary arteries

AimsWe sought to determine the diagnostic performance, clinical profiles and outcomes of anomalous aortic origin of coronary arteries (AAOCA) using a standardised echocardiographic approach in young adults and athletes.MethodsIn 2015–2019,...

Clinicopathological Characteristics and Prognosis of Squamous Cell Carcinoma of the Breast: A Population-Based Analysis

BackgroundTo better understand the clinicopathological features and prognostic profiles of squamous cell carcinoma (SCC) of the breast.MethodsInformation on breast cancer was obtained from the Surveillance, Epidemiology, and End Results database (2004–2016). Comparative analyses were carried out to investigate the heterogeneity in the clinicopathological characteristics and survival outcomes between SCC and invasive ductal carcinoma (IDC), while propensity score matching was conducted to analyze the variations among baseline characteristics. Prognostic factors for SCC of the breast were successively identified using Cox regression analysis.ResultsA total of 382 SCC patients and 561477 IDC patients were identified in this study. Comparatively, the SCC cohort exhibited a higher proportion of male individuals, poor differentiation, an advanced TNM stage, an increasing percentage of triple-negative (TN) subtype, an increasing rate of organ involvement, and less access to therapeutics. The aggressive profile was consistent in the TN subgroup, with a significantly higher proportion in SCC than in IDC (25.7% vs 6.8%). Prognosis of SCC was profoundly poorer than that of IDC (mOS, 78.6 months and 121.6 months, P < .0001; mBCSS 91.9 months vs 135.6 months, P < .0001), of which the inferior tendency remained stable among disease stage and therapeutic options, while no difference was detected in the 2 subgroups with the TN subtype. The 2-year survival rate was 66.9% and the 5-year survival rate was 51.4%, with the risk factors being older age, bilateral disease, advanced TNM stage, bone and visceral involvement, surgical intervention, radiation treatment, and chemotherapy.ConclusionsThis study systematically analyzed the heterogeneous characteristics of SCC of the breast in comparison with IDC. Squamous cell breast cancer presented with increasing aggressive behavior and inferior prognosis. Prospective studies should focus on this subgroup and introduce individualized therapeutic protocols in clinical practice.

Method of onabotulinumtoxin type A injection in chronic migraine: the PREEMPT protocol in clinical practice

Chronic migraine (CM), a condition where patients experience over 15 days of headache per month, was identified as a separate disease in the International Classification of Headache Disorders 3-beta version. Onabotulinumtoxin type A was approved for the treatment of CM in 2010 after the completion of the extensive PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) clinical program. The efficacy of onabotulinumtoxin type A was demonstrated in numerous studies in CM and medication-overuse headache. The paper focuses on the PREEMPT injection paradigm and provides guidance for successful and safe treatment of CM.

In vivo detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy.

Background: Magnetic resonance imaging (MRI) is indispensable for diagnosing neurological conditions such as multiple sclerosis (MS). MRI also supports decisions regarding the choice of disease-modifying drugs (DMDs). Determining in vivo tissue concentrations of DMDs has the potential to become an essential clinical tool for therapeutic drug monitoring (TDM). The aim here was to examine the feasibility of fluorine-19 (19F) MR methods to detect the fluorinated DMD teriflunomide (TF) during normal and pathological conditions.Methods: We used 19F MR spectroscopy to detect TF in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS) in vivo. Prior to the in vivo investigations we characterized the MR properties of TF in vitro. We studied the impact of pH and protein binding as well as MR contrast agents.Results: We could detect TF in vivo and could follow the 19F MR signal over different time points of disease. We quantified TF concentrations in different tissues using HPLC/MS and showed a significant correlation between ex vivo TF levels in serum and the ex vivo 19F MR signal.Conclusion: This study demonstrates the feasibility of 19F MR methods to detect TF during neuroinflammation in vivo. It also highlights the need for further technological developments in this field. The ultimate goal is to add 19F MR protocols to conventional 1H MRI protocols in clinical practice to guide therapy decisions.