Comparative Evaluation of the Efficacy of Hydrocortisone Suppository and Durvadi gudavarti in Raktarsha: A Management Protocol

The most common diagnosis for any anorectal complaint particularly of rectal bleeding in adults is haemorrhoidal disease. Regardless of grading conservative treatment is used primarily in symptomatic haemorrhoids. In Ayurveda, Sthanik Chikitsa (Local application) in the management of Arsha (Hemorrhoids) includes pralepa/pratisaran (Paste application). Instead of applying the lepa in the clinics by the clinician/proctologist, those formulations could be developed into Gudavarti (traditional suppository) & used in the management of Raktarsha (bleeding piles) for better compliance. Hence, development of ‘Durvadi Gudavarti’ using the indigenous medicinal herbs mentioned in Charaka Sanhita (Classical Ayurveda text) for pratisaran/pralepa in Raktarsha & its efficacy will be evaluated. Objectives: To study & compare the efficacy in patient treated with standard- Hydrocortisone suppository group & interventional- Durvadi Gudavarti group in the management of Raktarsha (Bleeding piles). Methodology: 130 patients of 2nd grade hemorrhoids will be selected and will be allocated into two equal groups by computer randomization. Experimental group will be treated with Durvadi Gudavarti & control group with Hydrocortisone based suppository for 2 weeks. Following Symptoms- PR Bleeding, Anal Pain, Prolapse of Pile mass/Lump, Anal pruritus, Mucous discharge & Constipation will be assessed subjectively and Size/ (Volume in cubic millimeter) of pile mass will be the objective parameter for study. Clinical evaluation will be done at Baseline and 3rd, 5th, 10th, 15th day after treatment onset. Proportion of patients that would respond clinically on 10th day will be the main end point, determined via disappearance of the clinical symptoms & more than or equal to 50 % reduction in the initial size of pile mass/lump. Time to response & need for any oral/ parenteral medication for pain, bleeding and constipation would be the secondary variables. Side effects (type, duration & severity) will be registered carefully. Expected Results: Durvadi Gudavarti contains indigenous herbs having anti-inflammatory, analgesic, haemostatic, wound healing, astringent, & laxative properties. Hence, it is expected to be as efficacious as Hydrocortisone suppository with lesser side effect in the management of Raktarsha. Results will be assessed on the basis of clinical assessment criteria using proper statistical values and tools. Changes will be observed in objective outcomes. Conclusion: Durvadi Gudavarti will be efficacious in the management of Raktarsha.

The multiple sclerosis patient’s journey model in Poland – future tasks

Improvement of the diagnostic and therapeutic processes and optimal use of resources in the context of health care system specificity accelerate the diagnosis and treatment onset, as well as improve the quality of life of patients with multiple sclerosis. International experience and data from clinical practice in Poland gave rise to a number of guidelines for the needed measures, from increasing the awareness about multiple sclerosis among the society and doctors in general, through expanding outpatient medical care, to proposing a model network of healthcare centres dedicated to patients with multiple sclerosis. It was pointed out that there is a need for a network of clinics specialised in the diagnosis and treatment of multiple sclerosis (MS clinics) and centres for comprehensive diagnosis and treatment, with a higher reference level and all the competences of an MS clinic, and, at the same time, providing both consultations in difficult clinical cases and access to the most advanced diagnostic and therapeutic methods. Attention was also drawn to the need to use modern e-health tools, which should improve the diagnostic and therapeutic process, as well as tighten the coordination of care by enabling an effective exchange of information between the patient and the entire interdisciplinary team involved in the therapeutic process.

Drug-induced parkinsonism

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Case Report: Early 68Ga-PSMA-PET Metabolic Assessment and Response to Systemic Treatment for First-Line Metastatic Clear Cell Renal Cell Carcinoma; About Two Clinical Cases

Early evaluation of response to anticancer treatment in metastatic renal cell carcinoma (RCC) is challenging as responses are sometimes delayed, as mixed responses can occur, and as conventional imaging have some limitations. As PSMA has been previously identified in neovasculature of clear cell RCC (ccRCC), 68Ga-PSMA-Positron Emitted Tomography (PET) could appear as an interesting tool to evaluate therapeutic response. We describe the association of an early decrease in 68Ga metabolism (at 8 weeks after treatment onset) and further radiological response (at 12 weeks after treatment onset) to treatment in two patients with different sensitivity to axitinib–pembrolizumab combination. Interestingly, one of these patients presented an initial progressive disease on pembrolizumab alone and a subsequent response to axitinib alone in the disease course; these response profiles were associated with absence of decrease and subsequent decrease in the 68Ga metabolism, respectively. Even if further prospective trials are needed, 68Ga-PSMA-PET may appear as a promising way for early prediction of response to ccRCC systemic treatment.

Seroconversion following COVID-19 vaccination: Can we optimize protective response in CD20-treated individuals?

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence COVID-19 severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor-seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6-monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment-onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B cell monitoring until (1-3%) B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small molecule anti-viral treatment to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.

Antibiotic Use in Term and Near-Term Newborns

OBJECTIVES We aimed to study whether national and local antibiotic stewardship projects have reduced the antibiotic use in newborns and to monitor potential changes in adverse outcomes. METHODS In a nationwide, population-based study from Norway, we included all hospital live births from 34 weeks' gestation (n = 282 046) during 2015 to 2019. The primary outcome was the proportion of newborns treated with antibiotics from 0 to 28 days after birth. The secondary outcomes were the overall duration of antibiotic treatment and by categories: culture-positive sepsis, clinical sepsis, and no sepsis. RESULTS A total of 7365 (2.6%) newborns received intravenous antibiotics during the period, with a reduction from 3.1% in 2015 to 2.2% in 2019 (30% decrease; P < .001). Hospitals with antibiotic stewardship projects experienced the largest reduction (48% vs 23%; P < .001). We found a small decrease in the median duration of antibiotic treatment in newborns without sepsis from 2.93 to 2.66 days (P = .011), and geographical variation was reduced during the study period. The overall number of days with antibiotic treatments was reduced by 37% from 2015 to 2019 (119.1 of 1000 vs 75.6 of 1000; P < .001). Sepsis was confirmed by blood culture in 206 newborns (incidence rate: 0.73 cases per 1000 live births). We found no increase in sepsis with treatment onset >72 hours of life, and sepsis-attributable deaths remained at a low level. CONCLUSIONS During the study period, a substantial decrease in the proportion of newborns treated with antibiotics was observed together with a decline in treatment duration for newborns without culture-positive sepsis.

Early cisternal fibrinolysis is more effective than rescue spasmolysis for the prevention of delayed infarction after subarachnoid haemorrhage

BackgroundTo compare the efficacy of two different concepts of cisternal therapy—PREVENTIVE fibrinolysis plus on-demand spasmolysis versus RESCUE spasmolysis—for the prevention of cerebral vasospasm (CVS) and delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid haemorrhage (aSAH).MethodsRetrospective analysis of 84 aSAH patients selected for cisternal therapy for DCI prevention. 66 high-risk patients received PREVENTIVE cisternal therapy to enhance blood clearance. Either stereotactic catheter ventriculocisternostomy (STX-VCS) or intraoperative placement of a cisterno-ventriculostomy catheter (CVC), followed by fibrinolytic cisternal lavage using urokinase was performed. In case of vasospasm, nimodipine was applied intrathecally. 22 low-risk patients who developed CVS against expectations were selected for STX-VCS as RESCUE intervention for cisternal spasmolysis with nimodipine. Rates of DCI and mean flow velocities of daily transcranial Doppler (TCD) ultrasonographies were evaluated.ResultsDespite a higher prespecified DCI risk, patients selected for PREVENTIVE intervention primarily aiming at blood clearance had a lower DCI rate compared with patients selected for intrathecal spasmolysis as a RESCUE therapy (11.3% vs 18.2%). After intrathecal treatment onset, CVS (TCD>160 cm/s) occurred in 45% of patients with PREVENTIVE and 77% of patients with RESCUE therapy (p=0.013). A stronger response of CVS to intrathecal nimodipine was observed in patients with PREVENTIVE intervention as the mean CVS duration after start of intrathecal nimodipine was 3.2 days compared with 5.8 days in patients with RESCUE therapy (p=0.026).ConclusionsPREVENTIVE cisternal therapy directed at blood clearance is more effective for the prevention of CVS and delayed infarction compared with cisternal RESCUE spasmolysis.Trial registration numberDRKS00016532.

A case series of 13 patients with COVID-19 associated respiratory symptoms treated with Nebulized OTR4120 (Cacipliq20®)

We report a series of 13 patients with COVID-19 treated with Cacipliq20®, an heparan sulfate mimetic approved for the treatment of hard to heal cutaneous ulcers. Heparan sulfates play important roles in tissue repair and possess antiviral activity. Cacipliq20® was administered through nebulization at a dose of 45 mg twice a day for 5.5 consecutive days. All patients presented respiratory symptoms with some dyspnea and in most cases pulmonary abnormalities on chest CT-Scan. Eight patients presented with a moderate form of the disease, three patients with a severe form, one with a mild form, and one with a critical form. In all patients the treatment was added to the standard of care. Ten patients were treated during the acute stage of the disease (<4 weeks from symptoms onset) while 3 patients were in the post-acute stage (>4 weeks from symptoms onset). A second treatment was administered for another 5.5 days in 6 patients. All patients showed clinically improvement after treatment. The time to first improvement ranged from 2 to 4 days after first treatment onset with a median of 3 days. Time to full clinical recovery ranged between 6 to 27 days from treatment onset with a median of 6 days. Lung CT scans followed clinical impression and showed a clear improvement of the lesions in most cases. The treatment was well tolerated in all patients. These preliminary observations should justify further evaluation through a well-designed placebo-controlled therapeutic trial.

Correlations between initial human-beta-defensin-1 level and quality of life of patients during anti-tuberculosis therapy

Background. The quality of life of patients with tuberculosis is an important component of the treatment effectiveness. Objective. To find the correlations between initial human-beta-defensin-1 (HBD-1) level and quality of life of patients during anti-tuberculosis therapy. Materials and methods. 100 patients with pulmonary tuberculosis were included in the study. The patients were diagnosed, treated and monitored according to current state protocols and World Health Organization guidelines. Additionally, the level if HBD-1 was measured in blood plasma by ELISA at the treatment onset. The patients were interviewed using SF-25 scale at the treatment inset, after 30 days and after 60 days. The parameters of physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, emotional-role functioning, and mental health were assessed. Results. We found correlations between the initial level of HBD-1 and quality of life parameters: physical functioning (-0.43), role-physical functioning (-0.34), bodily pain (-0.23), general health (-0.42), social functioning (-0.42), emotional-role functioning (-0.36); p<0.05. The obtained negative correlations indicate that a high initial level of HBD-1 is a predictor of lower quality of life during treatment. Conclusions. An increase in the level of HBD-1 at the treatment onset can be considered a predictor of a decrease in the quality of life during treatment in patients with pulmonary tuberculosis.