International Treatment Guidelines Research Articles

Hepatocellular carcinoma in hepatitis C virus patients treated with direct acting antivirals (DAAs) and patients not exposed to DAAs: a large center comparative study

BackgroundHepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system.ResultsGroup II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002).ConclusionOur study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC.

Manual therapists’ appraisal of optimal non-pharmacological conservative management of patients with lumbar spinal stenosis. An international Delphi study

BackgroundLumbar Spinal Stenosis (LSS) is a slow progressive degenerative disorder associated with chronic pain and disability. Although consensus-based international guidelines for invasive treatment of patients with LSS exist, few consensus-based guidelines for optimal conservative management strategies have been published. ObjectiveTo achieve manual therapists’ consensus on optimal physiotherapeutic management strategies for LSS. MethodsThe study employed a three-round, email–based International Delphi survey. All qualified members of the International Maitland Teacher Association (IMTA) (n = 30) were invited to participate. ResultsTwelve IMTA teachers participated in the study. Eight essential physiotherapy management strategies were identified, as follows: 1. Detailed assessment with in-depth interview; 2. Recognition of red flags, contraindications and precautions; 3. Neurological examination; 4. Postural and movement analysis with related ergonomics; 5. Functional analysis; 6. Individualized treatment based on assessment findings and research evidence; 7. Aerobic training and 8. Patient education. ConclusionThis Delphi survey provides a foundation for physiotherapists to individualize and optimise management approaches for patients with LSS. With a growing elderly population, there is an increasing need for evidence-based conservative management guidelines based on high quality research.

Budesonide Attains Its Wide Clinical Profile by Alternative Kinetics.

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis ("early intervention") became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma ("anti-inflammatory reliever", AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines.

Global perspectives on bipolar disorder treatment: in-depth comparative analysis of international guidelines for medication selection.

Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries. This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management. The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them. The variations in recommended drugs across guidelines arise from the approaches employed in guideline development - whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences. The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

Higher methadone dose at time of release from prison predicts linkage to maintenance treatment for people with HIV and opioid use disorder transitioning to the community in Malaysia

BackgroundIncarcerated people with HIV and opioid-dependence often experience poor post-release outcomes in the absence of methadone maintenance treatment (MMT). In a prospective trial, we assessed the impact of methadone dose achieved within prison on linkage to MMT after release. MethodsFrom 2010 to 2014, men with HIV (N = 212) and opioid dependence before incarceration were enrolled in MMT within 6 months of release from Malaysia's largest prison and followed for 12-months post-release. As a prospective trial, allocation to MMT was at random and later by preference design (predictive nonetheless). MMT dosing was individually targeted to minimally achieve 80 mg/day. Time-to-event analyses were conducted to model linkage to MMT after release. FindingsOf the 212 participants allocated to MMT, 98 (46 %) were prescribed higher dosages (≥80 mg/day) before release. Linkage to MMT after release occurred in 77 (36 %) participants and significantly higher for those prescribed higher dosages (46% vs 28 %; p = 0.011). Factors associated with higher MMT dosages were being married, on antiretroviral therapy, longer incarceration periods, having higher levels of depression, and methadone preference compared to randomization. After controlling for other variables, being prescribed higher methadone dosage (aHR: 2.53, 95 %CI: 1.42–4.49) was the only independent predictor of linkage to methadone after release. InterpretationHigher doses of methadone prescribed before release increased the likelihood of linkage to MMT after release. Methadone dosing should be introduced into international guidelines for treatment of opioid use disorder in prisons and further post-release benefits should be explored. FundingNational Institute of Drug Abuse (NIDA).

Non-Motor Symptom Management: Insights into Adherence to Treatment Guidelines in Parkinson's Disease Patients.

Non-motor symptoms (NMS) reduce quality of life in Parkinson's disease (PD) patients, who experience three times more NMS than individuals without PD. While there are international and national NMS treatment guidelines, their implication in clinical practice remains unclear. This study aimed to investigate the adherence to pharmacological NMS treatment guidelines in patients with mild to moderately severe PD. 220 PD patients with ≥1 NMS based on the Non-Motor Symptom Questionnaire and a Hoehn and Yahr stage ≤4 were randomly selected from the Swedish Parkinson registry and screened for inclusion. NMS were evaluated using the International Parkinson and Movement Disorder Society-Non-Motor Rating Scale (MDS-NMS), Parkinson's Disease Sleep Scale 2, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. Treatment was compared with Swedish national guidelines and international guidelines from the MDS Evidence-Based Medicine Committee. Among 165 included patients, the median number of NMS was 14, and in median 7 symptoms were estimated to require treatment. The most common NMS requiring treatment were pain (69%) and urinary problems (56%). Treatment of depression and constipation demonstrated the highest adherence to guidelines (79% and 77%), while dysphagia and excessive daytime sleepiness exhibited the lowest adherence (0% and 4%). On average, only 32% of NMS were treated in accordance with guidelines. Adherence to pharmacological guidelines for NMS in patients with mild to severe PD was low. This study highlights the need for improved evaluation and treatment of NMS to enhance symptom management and quality of life among PD patients.

Understanding how therapeutic exercise prescription changes outcomes important to patients with persistent non-specific low back pain: a realist review protocol

IntroductionPersistent low back pain (LBP) is the leading cause of disability worldwide, and therapeutic exercise is recommended as a first-line treatment in international guidelines. The effects of exercise on clinical outcomes of pain and physical function are small to moderate, despite broader impacts on cardiovascular systems, biological health, mood, and emotional well-being. Therapeutic exercise prescription is defined as exercise that is prescribed by a clinician for a health-related treatment. It is unknown how therapeutic exercise prescription creates effects on outcomes of importance. Realist reviews explore how underlying mechanisms (M) may be active in the context (C) of certain situations, settings, or populations to create an intended or unintended outcome (O). Our objective is to explore and understand the mechanisms by which therapeutic exercise prescription changes outcomes for people with persistent LBP.MethodsWe will develop initial programme theories based on preliminary data from a previous systematic review and consensus workshop. These theories will be modified with input from a steering group (experts), a stakeholder group (people with lived experience of exercise for persistent LBP and clinicians), and a scoping search of the published literature. An information specialist will design and undertake an iterative search strategy. These will be used to create CMO configurations, which will be refined and tested using the literature. The realist review will be reported following RAMESES guidance.DiscussionRealist reviews are uncommon in LBP research to date, yet those offer an opportunity to contrast with traditional methods of randomised controlled trials and systematic reviews and provide additional information regarding the contexts and mechanisms that may trigger certain outcomes. This can aid our understanding of the contextual features that may influence exercise prescription, such as for whom they are most effective, in what setting, how they are implemented and why. This realist synthesis will enhance our understanding of therapeutic exercise prescription to improve adherence and engagement and ultimately will provide clinically relevant recommendations regarding exercise prescription for those with persistent LBP.Systematic review registrationThe review has been registered with PROSPERO (CRD42017072023).

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI).

600 Background: Avelumab 1L maintenance is recommended as standard of care by international treatment guidelines for pts with aUC that has not progressed with 1L platinum-based chemotherapy, based on level 1 evidence from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). In the trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone (median OS, 23.8 vs 15.0 mo; HR, 0.76 [95% CI, 0.63-0.91]; 2-sided p=0.0036). The long-term safety of avelumab 1L maintenance was also demonstrated. It is estimated that 25% of the world’s population will have BMI ≥30 by 2035, and high BMI is a risk factor for bladder cancer. We report post hoc analyses of long-term outcomes from JAVELIN Bladder 100 in pts with high BMI (≥30) at baseline. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L platinum-based chemotherapy were randomized 1:1 to receive avelumab 10 mg/kg every 2 wk + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS; secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms. In the avelumab + BSC and BSC alone arms, 67 and 55 pts had high BMI at baseline, respectively. In these pts, median OS was 20.8 mo (95% CI, 16.9-34.4) with avelumab + BSC vs 12.7 mo (95% CI, 8.1-26.6) with BSC alone (HR, 0.77 [95% CI, 0.49-1.21]); 2-y OS rates were 47.8% vs 37.6%, respectively. Median PFS by investigator was 5.6 mo (95% CI, 3.7-7.5) with avelumab + BSC vs 2.1 mo (95% CI, 1.9-4.0) with BSC alone (HR, 0.64 [95% CI, 0.42-0.97]); 2-y PFS rates were 23.5% vs 11.3%, respectively. Long-term safety in pts with high BMI was generally consistent with the overall safety population (Table). Conclusions: This exploratory analysis shows the long-term efficacy and tolerability of avelumab 1L maintenance in pts with high BMI in JAVELIN Bladder 100, with no new safety concerns identified. These results further support the use of avelumab 1L maintenance as standard of care in pts with aUC who are progression free after 1L platinum-based chemotherapy, including pts with high BMI. Clinical trial information: NCT02603432 . [Table: see text]

Estimating the clinical and budgetary impact of using angiotensin receptor neprilysin inhibitor as first line therapy in patients with HFrEF.

Recent updates of international treatment guidelines for heart failure with reduced ejection fraction (HFrEF) differ regarding the use of angiotensin receptor neprilysin inhibitor (ARNI) as first-line treatment. The American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) 2022 guidelines gives ARNI a Class IA recommendation for HFrEF patients while the European Society of Cardiology's guidelines are less clear when ARNI could be considered as first line treatment option in de novo patients. This study aimed to model the clinical and budgetary outcomes of implementing these guidelines, comparing conservative ARNI prescription patterns with less conservative in Sweden and in the United Kingdom. A health economic model was developed to compare different treatment patterns for HFrEF. Incident cohorts were included on an annual basis and followed over 10years. The model included treatment specific all-cause mortality and hospitalization rates, as well as drug acquisition, monitoring, and hospitalization costs. Increasing the use of ARNI could lead to about 7000-12300 life years gained and 2600-4600 hospitalizations prevented in Sweden. These health benefits come with an additional cost of 112-195 million euros. Similar results were estimated for the United Kingdom, albeit on a larger population. Increasing the proportion of patients receiving ARNI instead of angiotensin converting enzyme inhibitors as first-line treatment of HFrEF will lead to a considerable number of additional life years gained and prevented hospitalizations but with additional cost in terms of health care expenditure in Sweden and in the United Kingdom.

Rapid Initiation of Antiretroviral Therapy with Coformulated Bictegravir, Emtricitabine, Tenofovir Alafenamide Versus Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in HIV-positive Men Who Have Sex with Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400-mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV(400-mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/ml) at 48 weeks per FDA Snapshot analysis. Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression; and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (p < 0.001), respectively, discontinued treatment due to adverse effects, death, or loss to follow-up. The median increase of CD4 count was 181 and 223 cells/μL (p = 0.020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < 0.001). BIC/FTC/TAF was more efficacious and safer than EFV(400-mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Qualitative Exploration of the Experiences of People Who Use Captagon and Therapists in Jordan

Background: Captagon (Fenethylline) is an amphetamine type stimulant (ATS) and one of the most popular substances of use in the Middle East. This study aims to describe and analyze the trajectory of captagon use, severity of addiction and withdrawal symptoms and its effect on quality of life from the perspectives of people who use captagon, who receive treatment as well as therapists. Methods: This study took a qualitative approach, using semi-structured, audio-recorded interviews, which were transcribed verbatim, translated to English and coded using Nvivo software for thematic analysis. Results: Data saturation was achieved after interviewing a total of 27 participants (7 therapists and 20 patients using captagon either alone or among other illicit drugs), most of which were male (n = 22). Their ages ranged between 18-48 years (median= 27). Four main themes were identified during the interviews: (1) Definition and sought effects of captagon; (2) the downside of captagon use and withdrawal symptoms associated with captagon use; (3) motivations for captagon use and to treatment; and (4) the impact of Covid-19 on captagon’s use and on treatment. Conclusion: This qualitative study has illustrated for the first time the several challenges and complicating factors that people who use captagon and therapists face in Jordan. Findings call attention to implementing effective interventions to raise public’s awareness of the negative impact of such use, with focus on high-risk groups, address the needs of different users and encourage the use of international treatment guidelines.

Gram negative bacteria related urinary tract infections: spectrum of antimicrobial resistance over 9 years in a University tertiary referral Hospital.

Overuse of antibiotics has led to an increase in antimicrobial resistance (AMR) worldwide, with a negative impact on the healthcare system and the patients. In this context, our study aims to assess the current AMR patterns of urinary tract infections (UTIs) associated to Gram-negative bacteria. Thus, we provide useful information for doctors dealing with prophylactic and therapeutic empiric therapies. We retrospectively analysed more than 650,000 urine cultures collected in the Microbiology Department of a referral University Hospital of Southern England from January 2014 to December 2022. AMR spectra for 164,059 Gram-negative associated (UTIs) were analysed. The lowest percentage of resistance was found for Amikacin (2.30%), Gentamicin (5.89%) and Co-Amoxiclav (10.49%). Over a 9-year time, there was no significant change in resistance to Amikacin (2.04% in 2014 compared to 2.18% in 2022; p = 0.602) and to Fosfomycin (11.50% in 2014 versus 16.65% in 2022; p = 0.577). Overall, the trend of AMR significantly rose for Cefalexin (17.96-18.42%; p < 0.0001), Co-amoxiclav (9.46-12.69%; p < 0.0001), Nitrofurantoin (10.20-14.18%; p < 0.0001) and Piperacillin/Tazobactam (14.52-18.96%; p < 0.0001). Gram-negative resistance spectrum towards Ciprofloxacin (11.83-9.01%; p < 0.0001), Gentamicin (6.29-5.26%; p < 0.0001), Pivmecillinam (26.88-11.02%; p < 0.0001), Trimethoprim (36.72-29.23%; p < 0.0001) and Ampicillin/Amoxicillin (65.20-57.99%; p < 0.0001) significantly decreased. Despite the application of national and international guidelines for prophylaxis and treatment of UTIs, the spectrum of resistance for the most common antibiotics is still changing. Clinicians in primary and secondary care must keep that in mind when prescribing antibiotics for suspected UTI and sepsis associated with Gram-negative infections Up-to-date therapeutic strategies can help implement treatment of UTI, reducing selection of multi-resistant pathogens and providing more accurate care for patients. Future studies will be required to help clinicians and keep the guidelines updated.

In Vivo Modeling of Complicated Necrotizing Enterocolitis

Introduction: There is no adequate and easily reproducible model of complicated necrotizing enterocolitis (NEC) that allows to study its etiopathogenesis and test various surgical treatment options in an experiment.Objective: To devise a method for in vivo modeling of complicated NEC using laparoscopy.Materials and methods: Our study was conducted at the premises of the Laboratory of Experimental Surgery and Oncology (Scientific Research Institute of Experimental Medicine, Kursk State Medical University) in compliance with international ethical standards and guidelines for humane animal treatment. Fifteen immature male rabbits underwent laparoscopy under inhalation anesthesia and then subserosal injection of damaging solutions (33% H2O2, 10% CaCl2, 4% KCl, 70% C2H5OH, 10% CH2O) into the intestinal wall. In 24 hours, we performed laparotomy, assessed pathological changes visually, and resected the section of the intestinal tube at the injection site. Then we performed a single­layer end­to­end intestinal anastomosis. Histological samples were made from a biopsy specimen. Morphological assessment of the changes was performed.Results: The most pronounced macro­ and microscopic changes were found in the animals injected with hydrogen peroxide. We assessed changes in the abdominal cavity 24 hours since the start of modeling and observed a pattern of partial intestinal obstruction and serous peritonitis. The morphological pattern was characterized by acute circulatory disorder in the intestinal wall with ulcerative necrotic defects and perforations.Conclusions: Based on morphological manifestations we devised a method for modeling complicated NEC using laparoscopy. It is easily reproducible in an in vivo experiment, close to the clinical situation, and allows to simulate typical morphological changes during severe NEC.

Current Evidence for the Use of HIPEC and Cytoreductive Surgery in Gastric Cancer Metastatic to the Peritoneum.

Gastric cancer (GCa) is an aggressive malignancy, representing the third leading cause of cancer mortality worldwide. The poor prognosis of GCa can be associated with the prevalence of peritoneal metastasis (PM). Current international and national GCa treatment guidelines only recommend palliative treatment options for patients with PM. Since the 1980s there have been multiple single arm trials, randomized controlled trials, and metanalysis investigating the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced GCa, with or without PM. Results from these studies have been encouraging, with some large-volume centers even incorporating HIPEC into their treatment algorithms for patients with advanced GCa. Additionally, there are several ongoing trials that, when completed, will increase our understanding of the efficacy of CRS & HIPEC in patients with GCa metastatic to the peritoneum. Herein we review the current evidence, ongoing trials, consensus guidelines, and future considerations regarding the use of CRS & HIPEC in patients suffering from GCa with PM.

Compliance with National and International Guidelines in the Treatment of Nonmotor Symptoms in Late-Stage Parkinson's Disease.

National as well as international Parkinson's disease (PD) treatment guidelines are available to guide clinicians. Previous research has shown that nonmotor symptoms (NMS) are pronounced in late-stage PD and has suggested that current treatment is insufficient and could be improved. The aim of this study was to investigate to which degree the national and international treatment guidelines are followed in the treatment of NMS in late-stage PD. This Swedish cohort was part of the Care of Late-Stage Parkinsonism (CLaSP) study. Late-stage PD was defined as Hoehn and Yahr stages IV-V in "on" and/or ≤50% on the Schwab and England Activities of Daily Living (ADL) scale. NMS were assessed with the NMS scale (NMSS), cognition with the Mini-Mental State Examination (MMSE), and depressive symptoms with the Geriatric Depression Scale (GDS-30). Symptomatic individuals were defined as ≥ 6 on an item of the NMSS; for dementia, a cutoff of ≤18 on the MMSE; for depression, a cutoff of ≥10 on the GDS. All 107 participants exhibited NMS to various degrees and severities; the median NMSS score was 91. Among symptomatic individuals, for depressive symptoms, 37/63 (59%) were treated with antidepressants; for hallucinations and delusions, 9/18 (50%) and 5/13 (38%) were treated with antipsychotics; and for dementia, 9/27 (33%) were treated with rivastigmine and 1 (4%) was treated with donepezil. For orthostatic hypotension, 11/19 (58%) with lightheadedness and 7/8 (88%) with fainting were treated with antihypotensives; for sialorrhea, 2/42 (5%) were treated with botulinum toxin; and for constipation, 19/35 (54%) were treated with laxatives. For insomnia, 4/16 (25%) were treated with hypnotics, and for daytime sleepiness, 1/29 (3%) was treated with psychostimulants. The present analyses suggest a need for clinicians to further screen for and treat NMS. Optimizing treatment of NMS according to the national and international treatment guidelines may improve symptomatology and enhance quality of life in late-stage PD.

Establishing a multi-specialty consensus in the clinical need for hypercholesterolemia management and its implication for patients access to innovative therapies.

Increased level of blood LDL-C has a causal and cumulative effect on advancing atherosclerotic cardiovascular diseases (ASCVD). European guidelines for treating high LDL-C levels have been recently updated. However, in France, several challenges (e.g., physician and patient awareness, healthcare management) limit the application of management guidelines. The aim of this study was to understand the current opinions and perceived unmet clinical needs in recognising and managing hypercholesterolemia as an ASCVD risk factor, and to explore consensus around factors that support the effective management of elevated LDL-C. An expert group of cardiologists, endocrinologists, biology/genetics researchers, and a health technology assessments expert, from France was convened. The current management of hypercholesterolemia and barriers to achieving LDL-C goals in France were discussed and 44 statements were developed. Wider consensus was assessed by sending the statements as a 4-point Likert Scale questionnaire to cardiologists and endocrinologists across France. The consensus threshold was defined as ≥75%. A total of 101 responses were received. Consensus was very high (>90%) in 25 (57%) statements, high (≥75%) in 18 (41%) statements and was not achieved (<75%) only in 1 (2%) of statements. Overall, 43 statements achieved consensus. Based on consensus levels, key recommendations for improving current guidelines and approaches to care have been developed. Implementation of these recommendations will lead to better concordance with international treatment guidelines and increase levels of education for healthcare practitioners and patients. In turn, this will improve the available treatment pathways for cardiovascular diseases, potentially creating improved patient outcomes in the future.

Assessment of knowledge, attitude, and practice of primary healthcare physicians in Qatar towards hypertension management: An online cross-sectional study.

Primary health care is integral to diagnosing and managing hypertension. This study aimed to assess the knowledge, attitude, practice, priority, and confidence of primary care physicians in Qatar toward hypertension diagnosis and management, and to measure the determinants of good knowledge, desirable attitudes, and desirable practices. We conducted a cross-sectional web-based survey using a modified version of the World Hypertension League Questionnaire during the period from August 30th to October 23rd, 2020. All primary care physicians working in any of Qatar's 27 publicly run primary healthcare centers were invited to participate in the survey. Out of the 450 primary care physicians working at that time, 197 completed the study questionnaire with a response rate of 43.8%. Most respondents stated that they followed local or international treatment guidelines for hypertension management (96.4%). Primary care physicians were highly confident and prioritized hypertension management. The overall desirable practice score was 73.8%, with the highest score (95.4%) for assessing adherence to antihypertensive medications, whereas the lowest desirable practice score was 33.5% for counseling on home blood pressure monitoring. Fifty-one-point eight percentage and 62.4% correctly identified 140 mm Hg and 90 mm Hg as the systolic and diastolic blood pressure threshold for diagnosing hypertension in most patients. The lowest knowledge scores were for hypertension epidemiology in Qatar and recommended dietary modification for hypertensive patients. Respondents had positive attitudes toward task sharing with nonphysician healthcare workers for most items (58.9%-78.2%), except for drug prescriptions (30.5%). Primary care physicians in Qatar had positive attitudes, with high overall confidence and conviction (priority) scores toward hypertension. However, their knowledge scores and certain practices were suboptimal. Healthcare policymakers in Qatar should raise primary care physicians awareness of the current burden of untreated hypertension in the country by organizing targeted educational programs and emphasizing the importance of following national clinical practice guidelines in the diagnosis and management of hypertension.

Prevention of Radiographic Progression in Higher-Risk Patients with Rheumatoid Arthritis Using Filgotinib in PhaseIII Studies: Narrative Review of PostHoc Analyses.

Filgotinib is an oral preferential Janus kinase1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH1) and vs MTX in MTX-naïve patients with RA (FINCH3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from posthoc analyses of phase3 trials of filgotinib that examined subgroups with 4PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.

915 Obturator Hernia: A Case Report of Intestinal Obstruction in a 79yo Male with Challenging Diagnosis and Non-Standardised Treatment

Abstract Introduction Obturator Hernia (OH) is a rare condition that accounts for &amp;lt;1% of all abdominal wall hernias but is associated with the highest mortality and morbidity. OH in men are especially rare, with a male:female ratio of 1:14. Early surgical intervention is often delayed due to clinical and radiological diagnostic difficulties. At present, there are no international guidelines for treatment or best surgical approach to manage this condition. Case Presentation We present the case of an emaciated 79-year-old male with a 12-day history of right iliac fossa pain radiating to the right thigh, with a 2-day history of absolute constipation, vomiting and significant weight loss. This patient had a surgical history of elective right open inguinal hernia, on background of moderate-COPD. CT imaging revealed small bowel obstruction secondary to a small right obturator hernia containing a loop of small bowel. The patient underwent an exploratory laparotomy with intra-operative findings of 1cm defect in the right obturator foramen containing viable small bowel with incidental finding of right-sided femoral hernia; both defects corrected with PDS interrupted sutures. Iatrogenic perforation of the small bowel during hernia-reduction resulted in small bowel resection with primary anastomosis. The patient developed ileus requiring TPN post-operatively. During follow-up, there was no evidence of recurrence or further complications. Conclusion OH diagnosis is challenging owing to its rarity and non-specific presentation. Surgical intervention is the only definitive management for OH, thus awareness of this condition is crucial to allow an earlier approach and attempt to mitigate the associated high morbidity and mortality rates.

Recommendations for the healthcare of patients with FOP

Fibrodysplasia ossificans progressiva (FOP) is avery rare, severe genetic disorder triggered by again-of-function mutation in the ACVR1 gene that codes for the typeI bone morphogenetic protein (BMP) receptor ACVR1 (activinAreceptor-type1), also known as ALK2 (activin receptor-like kinase-2). It leads to the onset and progression of heterotopic ossification (HO) in soft and connective tissue. HO is often preceded by episodes of soft tissue swelling or flare-ups. Flare-ups, characteristic of FOP, may be induced by trauma, infection, vaccination, or other medications, as well as surgical procedures or may occur spontaneously. As patients age, they develop severe mobility limitations due to progressive HO formation, including immobility, causing ashortened life expectancy. FOP's first characteristic clinical sign is the congenital malformation of one or both big toes with valgus axis deviation, which is present in almost all patients. To confirm the diagnosis, molecular genetic analysis of the ACVR1 gene is possible. This white paper aims to provide an overview of the necessary prerequisites and conditions for the care of patients with FOP and positively contribute to patients with FOP by improving the overall availability of knowledge. To achieve this, relevant aspects of the care of the very rare disease FOP are presented, from the initial diagnosis to the care in regular care based on the authors' knowledge (German FOP network) and the international FOP Treatment Guidelines. The recommendations presented here are addressed to all actors and decision-makers in the health care system and are also intended to inform patients and the public.