Good Clinical Practice Guidelines Research Articles

Elektronska komunikacija u porodičnoj medicini

Traditional communication between physicians and patients consists of verbal and non-verbal communication. Non-verbal communication can emphasize, modify, or supplement a message that is verbally conveyed and reduce the possibility of misunderstanding. Web applications offer the ability to communicate with physicians and patients outside the healthcare facility. E-mail communication of the selected physician and patient is defined as electronic communication of doctors and patients in a contractual relationship in which the health information provider bears responsibility for the patient's health as his or her chosen physician. A literature review was conducted based on European and American studies reports to determine whether the use of electronic communication in family medicine could contribute to improving the quality of health care. The search for PUBMED, BMJ, JMIR and OVID was performed using the terms: electronic communication, family medicine, email, physician, patient. The most important benefits of electronic communication in family medicine are the simplicity and increased efficiency of communication, the expansion of resources and the ability to communicate, saving time and the ability to print electronic messages. The disadvantages lie in the potential compromise of confidentiality, the lack of monetary compensation and overload of the doctors, the potential for miscommunication, diagnostic error and unrealistic user expectations. Information technology must not replace traditional physician-patient communication. Although the results of the available studies have not provided strong enough evidence to broaden the introduction of electronic communications into everyday practice, adhering to the guidelines of good clinical practice, email and other forms of internet communication could contribute to improving the quality of primary care.

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry)

IntroductionClozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited...

The revamped Good Clinical Practice E6(R3) guideline: Profound changes in principles and practice!

The International Council for Harmonisation has released a draft version E6(R3) of the Good Clinical Practice Guideline for public consultation. The objective of the revamped guideline is to make the new provisions applicable across diverse clinical trial types and settings and to remain relevant as technological and methodological advances occur. E6(R3) includes profound changes in the structure and content of E6(R2) version, which will impact all the trial conduct processes from planning to reporting. This guideline's focus on principles, digital technology, ethics, and quality will increase the responsibilities of the ethics committees, the investigator, and the sponsor. This brief review discusses the impact of the guideline on trial conduct and the challenges of implementation in India.

A Comprehensive Review: Chronic Pain Sequelae in the Presence of Ehlers-Danlos Syndrome.

Patients diagnosed with Ehlers-Danlos syndromes (EDS), and especially those with the hypermobility subtype, often experience a diverse range of acute and chronic pain conditions throughout their lifetime. These can present in a variety of different phenotypes and comorbidities, making it difficult to develop structured treatment protocols. This review seeks to summarize the current literature to address old and novel treatments for EDS. Historically, medications and surgery have been used to treat patients with EDS but with low efficacy. Newer therapies that have shown promising effects for both decreasing pain and increasing quality of life include physical/occupational therapy, transcutaneous electrical nerve stimulation units, trigger point injections, low-dose naltrexone, and laser therapy. In addition, addressing the psychosocial aspects of pain with EDS through methods like cognitive behavioral therapy and patient education has shown to be vital in minimizing pain. Most research also emphasizes that pain management should not only focus on pain reduction, but on helping reduce symptoms of hypermobility, central sensitization, and fatigue to make an impactful difference. Research on pain in EDS is still limited with good clinical practice guidelines often limited by poor sample size and lack of clinical studies. Treatment options should be structured based on the specific type of pain pathology and presenting symptoms of each patient and their comorbidities. Future research should attempt to prioritize larger sample sizes, clear definitions of EDS subtypes, randomized trials for treatment efficacy, and more studies dedicated to non-musculoskeletal forms of pain.

Withdrawing Antipsychotics for Challenging Behaviours in Adults with Intellectual Disabilities: Experiences and Views of Experts by Experience.

People with intellectual disabilities (PwID) are frequently prescribed long-term antipsychotics for behaviours that challenge (BtC) despite the lack of proven effectiveness and the increased risks for side effects of these medications in this population. National and international good clinical practice guidelines recommend deprescribing antipsychotics for BtC, which is often not successful due to environmental and other factors. The involvement of all stakeholders, including PwID, is crucial for deprescribing. However, studies showed that PwID and/or their families are often not involved in decision-making regarding the (de)prescribing of antipsychotics despite their desire to get involved. Moreover, studies on the views of PwID regarding their experiences of withdrawing from antipsychotics are lacking. The aim of this study was to gain insight into the views of PwID by investigating their experiences of discontinuation of long-term prescribed antipsychotics for BtC. A qualitative study was set up. Seven experts by experience with mild intellectual disabilities were interviewed. After six interviews, data saturation was achieved. Interviews were transcribed verbatim. Using phenomenological analysis, themes on lived experiences were extracted. Each consecutive interview was analysed. The four main themes extracted from the interviews were the quality of treatment, knowledge and information about psychotropics and the process of withdrawal, support from the participants' environment and the coping style of the interviewees themselves.

Cellular Immune Composition in Multiple Myeloma Patients Associated with Variable Humoral Responses to Sars-Cov-2 Vaccination

Background: Multiple Myeloma (MM) patients are immune-deficient and mount suboptimal immune responses to SARS-CoV-2 mRNA vaccine, making them more susceptible to severe COVID-19 manifestations. We have previously described that MM patients undergoing certain therapies have compromised humoral immune responses even after receiving multiple doses of the SARS-CoV-2 mRNA vaccine (Aleman, et al. Cancer Cell 2022). However, the mechanisms underlying the suboptimal antibody responses observed in these patients are not understood. Emerging research suggests that specific cell populations within the immune milieu, such as Follicular helper (TFH) CD4+ T cells, help B cells mount a robust serological response (Cui, et al. 2021). In addition, Natural Killer (NK) cells have been known to play a protective role in SARS-CoV-2 infection (Fuentes-Villalobos, et al. 2022). We report here on the cellular immune composition highly associated with suboptimal humoral immune responses in MM patients. Methods: We longitudinally followed 31 MM patients with variable serological responses after receiving SARS-CoV-2 vaccination, as determined by quantification of anti-spike IgG antibody titers, and compared to 13 age matched healthy donors. We categorized patients based on their production of anti-spike IgG post full vaccination of two doses. Of our selected cohort, 14 patients had failed to produce detectable anti-spike IgG (MM sub-optimal), whereas the other 17 MM patients had detectable anti-spike IgG (MM within detectable range). We analyzed samples collected post second dose and post third dose of COVID-19 vaccine using high dimensional spectral flow cytometry to elucidate immune phenotypic differences. Data and sample collection for this study was approved by the institutional review board (IRB) and follows the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice (IRB: GCO#: 16-00791 (MM patients) & GCO #: 20-03374 (PARIS). Results: We compared spike binding antibody responses pre and post third vaccine dose in our MM and control cohorts. While the third dose of mRNA vaccine resulted in a robust increase in anti-spike IgG for the majority of patients, the serological response in MM patients remained significantly lower (p<0.05) as compared to healthy controls (Figure 1A). The sub-optimal MM patient group had the lowest serological response, with 28% (4/14) of the patients showing no detectable anti-spike IgG levels post third booster vaccination. MM patients with sub-optimal responses did not have an increased incidence of lymphopenia or difference of absolute B cell and T cell counts. Further examination, however, revealed noticeable differences in TFH and NK cell populations. Sub-optimal MM patients showed a significantly lower prevalence of PD1+CXCR5+ TFH cells (p<0.01), as compared to MM patients within detectable serological range both pre and post third vaccination (Figure 1B). PD1+CXCR5+ TFH cells are associated with higher levels of anti-spike IgG neutralizing antibodies (Cui, et al. 2021). In addition, sub-optimal MM patients showed significantly fewer NK cells (p<0.05) when compared to MM patients within detectable serological range and healthy donors (Figure 1B). NK cell subset analysis in the sub-optimal MM patient group revealed a high prevalence of immature NK cell subsets (CD16-/dimCD56hi) (p<0.01), whereas MM patients within serological range and healthy donors showed a dominant mature cytolytic NK cell subset (CD16hiCD56dim). Half of the sub-optimal MM patients were on anti-CD38 monoclonal antibody therapy (7/14) compared to those mounting efficient responses (11%, 2/17), which we have previously described as affecting anti-spike IgG production and depleting NK populations. Conclusion: We describe here that significantly reduced numbers of CD4+ TFH and NK cells is associated with sub-optimal serological responses to SARS-COV-2 mRNA vaccination in MM patients. The distinct phenotype observed in our sub-optimal MM patient cohort could be a product of their pre-existing immune composition, the nature of their disease progression, or in response to ongoing therapies. Our data suggests that longitudinal immunophenotyping may identify vulnerable MM patients that may need additional vaccinations or prophylactic intervention, such as monoclonal antibody therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Salvage with Sequential T Cell Redirection for Myeloma Patients Who Have Previously Progressed on T Cell Directed Therapy Is Associated with Significant Cellular Activation of the Immune Microenvironment

Background: With the recent approval of two anti-BCMA CAR-Ts and multiple anti-BCMA and anti-GPRC5D bispecific antibodies (BiAbs) in clinical trials, rational salvage strategies for patients who progress after these therapies is an area of unmet need in multiple myeloma. We have previously reported favorable outcomes for patients receiving sequential T cell directed therapies with depth of response and progression free survival (PFS) (Mouhieddine et al Blood (2021) 138 (Supplement 1: 821). However, the underlying immune mechanisms are not well known and would be essential to design sequential strategies combining different T cell directed therapies. Here we show that sequential T cell mediated therapies promote not only T cell engagement but also immune activation in natural killer (NK) and dendritic cells (DC) cellular subsets in patients with relapsed/refractory multiple myeloma (RRMM). Methods: We identified 15 RRMM patients who had progressed on a T cell directed therapy, either anti-BCMA CAR-T (n=10) or BiAbs (n=5) and then received another BiAb as a subsequent line of therapy. 70% of patients who progressed on anti-BCMA CAR-T (7/10) and 20% who progressed on BiAbs had interim therapies before receiving subsequent BiAbs therapy. The median time between the first T cell directed therapy and subsequent therapy was 5 months (range 0- 26 months). We profiled immune cell activation in peripheral blood (PB) by high dimensional flow cytometry and Olink Proteomics. Clinical data such as patient demographics, disease characteristics and post-clinical trial outcomes were collected retrospectively until July of 2022. Data and sample collection for this study was approved by the institutional review board (IRB) and follows the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice (IRB: GCO#: 11-1433 & GCO #: 18-00456). Results: We compared baseline immune cell populations of 15 RRMM patients in the PB post relapse on T cell mediated therapy and during subsequent BiAb treatment (Figure 1a). 93% of patients (14/15) received BiAbs therapy with a different target than their first T cell directed regimen. 73% of patients (11/15) received sequential BiAbs therapy in combination with an anti-CD38 monoclonal antibody. Patients had a median age of 63 years (range 43-89) at time of progression after the first T cell directed therapy. MM patients were heavily pre-treated with a median of 6 prior lines of therapy (range 3-16). All patients were triple-class refractory while 66% were penta-drug refractory. Immune profiling at time of progression on the first T cell directed therapy, was associated with increased expression of exhaustion markers on CD4+ and CD8+ T cells. Treatment with a second BiAb was associated with significant re-activation of endogenous T cells. Specifically, CD8+ T cells demonstrated increased expression of hallmark surface activation markers such as HLA-DR and CD69+ (p<0.05, Figure 1b), and this increase was consistent in CD4+ T cells as well (p<0.01, Figure 1b). Alongside T cell engagement we saw an increase in surface activation markers CD69+ and HLA-DR on NK and DC populations respectively (p<0.01). This indicates that the application of the second T cell directed therapy not only reactivates T cell compartment but potentiates widespread immune cell activation. Plasma cytokine analysis from these patients revealed elevated CXCL10, CXCL9, and TNFa during bispecific therapy; reinforcing the activation state of the patients during treatment. Although the CD4:CD8 ratios remain conserved, we observed a significant differentiation of CD8+ T cells through sequential therapy, with a reduction of naïve CD8+ T cells (p=0.022) and increase of effector memory CD8+ T cells (p<0.01). Conclusion: Our data suggests that patients who progressed on T cell directed therapy and went on to receive T cell mediated BiAbs, not only respond clinically, but also have hallmark expression of activation markers. T cells can be reactivated post relapse from T cell mediated therapies, indicating that T cell targeted treatments can be applied successfully in sequential order with favorable patient outcomes. We are currently performing immune profiling on more PB and bone marrow samples to further confirm these findings in a larger patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluating the feasibility, effectiveness and costs of implementing person-centred follow-up care for childhood cancer survivors in four European countries: the PanCareFollowUp Care prospective cohort study protocol

IntroductionLong-term survival after childhood cancer often comes at the expense of late, adverse health conditions. However, survivorship care is frequently not available for adult survivors in Europe. The PanCareFollowUp Consortium...

AYURVEDIC MANAGEMENT OF GRIDHRASI WITH SPECIAL REFERENCE TO SCIATICA: A CASE REPORT

Background: Gridhrasi is one of the most common disorders of Vata Dosha described in Ayurveda classics according to sign and symptom it can be related to sciatica. Sciatica is characterized by pain &amp; discomfort associated with the pathology of sciatic nerve root in people. It is associated with Low back pain, pain radiates to lower limb till toes, tingling and numbness sensation in the buttock region. This is an epidemic disease of modern era with industrial region and more common with office workers. Methodology: The present case study was carried out by following good clinical practice guidelines, studies on Gridhrasi and Ayurveda textual references. Written informed consent of the patient was taken before starting the treatment. A detailed patient history with all necessary clinical and physical examination and laboratory investigations were carried out. This is a single case study. A 49-year-old male patient presented with the complaint of low back pain radiating to left lower limb, tenderness at L4 and L5 region difficulty in walking for long distance and with associated symptom like fever, cough and cold. Sahacharadi Kashayam, Dhanwataram 101 Avarthi, Vyoshadi Vatakam, Dasamoolakadutrayam Kashayam were given for 20 days along with external therapy. Result and conclusion: After 20 days of treatment there was significant changes in subjective and Objective parameter of patient like reduction in pain (VAS scale), tenderness, &amp; other symptoms.

Validity and Tolerability of Awake Calibration of an Accelerometer Neuromuscular Monitor.

Validity and Tolerability of Awake Calibration of an Accelerometer Neuromuscular Monitor.

Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials

During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients.

Early Results using a Locking Intramedullary Nail for Charcot Reconstruction

Category: Other; Basic Sciences/Biologics; Diabetes; Hindfoot; Trauma Introduction/Purpose: The goal for this review was to show the early results from a novel locking intramedullary nail within the medial column for use in the reconstruction of Charcot arthropathy. We hypothesized that the utilization of the locking intramedullary nail would lead to successful fusion and stabilization. Our primary aim was to assess the rate of fusion, with secondary aims of an acceptable reduction between pre- and postoperative Meary's angle, time to return to function, and safety. Methods: This case series was designed and implemented by JL and AM. Informed consent was obtained from all patients to allow their clinical data and images to be used for research. The authors examined all patients, collected all data for the study, and performed all surgical procedures at their respective sites. Additional patients were included from Carroll Jones, MD and W. Hodges Davis, MD. All chart and radiographic reviews were also performed by JL and AM. The Advarra Institutional Review Board (IRB; Columbia, MD) determined that this research was exempt from IRB oversight. This study was conducted in compliance with the ethical principles from the 1964 Declaration of Helsinki and the International Conference on Harmonisation guidelines for Good Clinical Practice, along with the latest Health Insurance Portability and Accountability Act (HIPAA) regulations. Results: With respect to safety, there were no intraoperative complications. Additionally, there were no instances of recurrent ulceration in those patients who had ulcerations preoperatively. There were no instances of hardware failure or limb loss in the case series. There were 3 adverse events (21.43%), all of which are to be considered major events that required operative intervention for resolution. There were 2 instances of wound dehiscence (14.29%) that required operative debridement and 1 instance of a stable partial nonunion along the medial column (7.14%) which was a braceable deformity (Table 3). Conclusion: Overall, this case series review of the use of a locking intramedullary nail in Charcot neuroarthropathy patients showed efficacy by rate fusion and time to weightbearing and safety by the low number of adverse events. The data show that the utilization of the locking intramedullary nail can lead to successful fusion and stabilization, even in these high-risk patients.

Physical fitness in children and adolescents with inflammatory bowel disease: protocol for a case–control study

IntroductionInflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract, associated with adverse health consequences that may adversely influence physical activity and body composition in youth. These effects...

Rationale and Protocol of the Multimodality Evaluation of Antibody-Mediated Injury in Heart Transplantation (LEONE-HT) Observational Cross-Sectional Study.

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies. Methods and analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses. Ethics and dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology.

EFFECTIVE MANAGEMENT OF ARTAVA KSHAYA BY AYURVEDA TREATMENT: A CASE REPORT

Artava Kashaya is the condition in which menstruation does not occur at the appropriate time, which can be correlated with oligomenorrhea with scanty menstrual blood flow. The principle of treatment is focused on Agni Deepana, Sroto Shodhan, Artava Pravartana and Vata Kapha Shaman. Hence in the current case report treatment scenario was selected for the management and follow-up was done every 15 days. The present case study was carried out by following good clinical practice guidelines, studies on irregular menstruation, and Ayurveda textual references. Written informed consent of the patient was taken before starting the treatment. A detailed history of the patient with all necessary clinical and physical examination and laboratory investigations were carried out. The patient had got her menstruation regularly with normal duration while taking medicine. Also, the amount of flow was improved, and the intensity of pain was reduced effectively from moderate to mild. Even after the cessation of medicine, she got her menstruation in 30 days with a normal amount of flow. Hence, the most common gynecological problem in adolescent girls is mostly amenorrhea or menorrhagia due to frequent ovulation that can be triggered by the presence of oligomenorrhoea which is a physiological condition after menarche, and which usually happens after a period of a regular cycle. Therefore, Artava Kshaya can be correlated with oligomenorrhoea or hypomenorrhea. Artava Kshaya is explained by Acharya Sushruta in Sushrut Samhita Sutra sthan chapter 15 with the characteristics of Yathochit Akal Darshan with Alpartava and sometimes featured with Yoni Vedana.

Rationale and Design of a Randomized Controlled Trial of Bivalirudin with a Prolonged High-Dose Infusion Versus Heparin Monotherapy During Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction: The BRIGHT-4 Trial

Intravenous anticoagulant therapy is critical to prevent ischemic events without increasing the risk of bleeding in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Heparin and bivalirudin are the most commonly used adjunctive anticoagulant agents during PPCI. However, the superiority of the 2 most optimal regimens with these agents in patients undergoing PPCI remains controversial. The BivaliRudin with prolonged high-dose Infusion durinG PPCI versus Heparin Trial 4 (BRIGHT-4) is a large-scale, prospective, multicenter, active-control, parallel-group, open-label, randomized trial designed to test whether bivalirudin with a post-PCI high-dose infusion is superior to heparin monotherapy in STEMI patients undergoing PPCI. A total of 6000 patients will be enrolled and randomly assigned to receive bivalirudin or heparin in a 1:1 ratio. Patients allocated to the bivalirudin group will be treated with a high-dose bivalirudin infusion (1.75 mg/(kg·h)) after PCI for 2 to 4 hours. In the heparin group, the use of glycoprotein IIb/IIIa inhibitors will be reserved for the development of procedural thrombotic complications. The efficacy and safety of bivalirudin will be evaluated at 30 days, 6 months, and 12 months after the randomization. The primary endpoint is a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding at 30 days after randomization. The BRIGHT-4 study protocol has received approval from the ethics committee of General Hospital of Northern Theater Command (Shenyang, China). The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal (Trial registration number: NCT03822975).

Stakeholders’ views on the most and least helpful aspects of the ICH E6 GCP guideline and their aspirations for the revision of ICH E6(R2)

BackgroundThe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has published the ICH E6(R2) Good Clinical Practice (GCP) guideline, which provides standards for the design, conduct, documentation, and reporting of clinical trials. Revision to E6(R2) is currently underway, aiming to adapt the guidance to the current regulatory environment. The Clinical Trials Transformation Initiative (CTTI) interviewed stakeholders, gathering their experiences implementing ICH E6 GCP and suggestions for revising the guidance. MethodsWe conducted a qualitative descriptive study using in-depth interviews. Participants were purposefully selected to ensure diversity in geography, research role, and type of institution. Participants reflected on their aspirations for the ICH E6 GCP revision and described sections of the guidance that they found most and least helpful. Narratives were analyzed using applied thematic analysis. ResultsMany participants found ICH E6 GCP generally clear and helpful. They appreciated that the guidance is globally accepted and serves as a common standard for research worldwide. Participants also noted opportunities for improvement, suggesting that the revised guidance should incorporate flexibility, simplify requirements, and accommodate advances in research conduct. They highlighted areas where language should be updated and concepts clarified and expressed a desire for transparency and inclusiveness in the revision process. ConclusionOur findings show that many participants view the ICH E6(R2) guidance as helpful overall, although substantial room for improvement remains. We have provided the full report of these findings to ICH in hopes that it will be useful as the E6 GCP guideline is revised.

COVID-19 vaccination antibody responses in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria

COVID-19 vaccination antibody responses in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria

Effectiveness of multimodal exercises integrated with cognitive-behavioral therapy in working patients with chronic neck pain: protocol of a randomized controlled trial with 1-year follow-up

BackgroundThe etiology of neck pain is multifactorial and includes personal and work-related factors such as age, sex, wrong postures, and repeated strains. Studies based on bio-psychosocial model also link chronic neck pain to psychological factors. Over time, the use of multidisciplinary interventions for chronic neck pain has grown in order to improve disability, pain, and adaptive cognitions and behaviors towards patients’ problems. The objective is to evaluate the effectiveness of an individual-based multidisciplinary rehabilitation program that integrates cognitive-behavioral therapy focused on kinesiophobia with specific exercises in the treatment of patients with chronic neck pain, employed in different working activities.MethodsA randomized, parallel-group superiority-controlled trial will be conducted with 1-year follow-up. One hundred seventy patients engaged in several working activities (blue collar and white collar workers) will be randomly allocated to either the experimental (receiving a multidisciplinary rehabilitation program combining multimodal exercises with psychologist-lead cognitive-behavioral therapy sessions) or the control group (receiving general care physiotherapy). Both groups will follow individual-based programs once a week for 10 weeks. The main outcome measures will be the Neck Disability Index, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, a pain numerical rating scale, the Short-Form Health Survey, and the Work Ability Index. Participants will be evaluated before, after training, and after 12 months.DiscussionFindings may provide empirical evidence on the effectiveness of an individual-based multidisciplinary rehabilitation program on inducing clinically significant and long-term improvements in the disability, pain, psychological factors, and quality of life of workers with chronic neck pain and that these would be maintained in the long term. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities’ recommendations.Trial registrationClinicalTrials.gov NCT04768790. Registered on 24 February 2021

Seizure prophylaxis following aneurysmal subarachnoid haemorrhage (SPSAH): study protocol for a multicentre randomised placebo-controlled trial of short-term sodium valproate prophylaxis in patients with acute subarachnoid haemorrhage

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial....