What role can a homoeopathic psychiatrist play in restoring mental health in an unequal world?

World Mental Health Day, observed on the 10 October, is an occasion for the mental health professionals to dedicate themselves to bringing succour to the numerous persons suffering from mental health disorders. The World Mental Health Federation has declared this year’s theme as ‘Mental Health in an Unequal world.’ The call is timely considering the distress wrought on different communities due to the pandemic and the social and economic distress which has affected all sections of the population, albeit with different intensities causing differing impacts. The article explores the theme in the historical context and outlines the various concerns which mental health professionals should concern themselves with. It is a common knowledge that they are in short supply all over the world. Homoeopaths, due to their approach to health, disease and individuals are uniquely equipped to fill this gap and thus make a difference. There are very few examples, at the institutional level, where community-based activities addressing the mental health issues have been successfully undertaken and have made an impact. The article draws on the almost two-decade-long experience of the Department of Homoeopathic Psychiatry, Dr. M. L. Dhawale Memorial Homoeopathic Institute in this area, thereby illustrating the possibility of incorporating similar practices in the District Mental Health Programme. Clinical activity needs to be reported in peer-reviewed journals and initiating research in priority areas would help homoeopathy to be recognised as a discipline which can be a part of Integrated Mental Health Care for mental disorders.

An educational approach for early student self-assessment in clinical periodontology

Background Self-assessment is a mandated educational requirement for use in dental undergraduate programmes. It is weakly supported for use in early clinical training and studies are criticized for the conceptual and methodology shortfalls. The aim of the study was to compare the alignment of student self-assessment to both staff assessment and written exams in early clinical training using an educational approach. Methods In 2014-2015, 55 third-year dental students completed three educational sessions comprising of (a) classroom teaching (lecture, video) with post-lesson written exam and (b) clinical activity with student self-assessment, staff assessment and student reflection. An intra-individual analysis approach, staff validation, and student scoring standardization were implemented. Cognitive (clinical competency) and non-cognitive (professionalism) items were separated in the analyses. Results There were medium correlations (Spearman’s rho, r) between student self-assessment and staff assessment scores for cognitive items (r, 0.32) and for non-cognitive items (r, 0.44) for all three combined sessions. There were large correlations for individual sessions. Compared to the post-lesson written exam, students showed small correlation (r, 0.22, 0.29) and staff showed medium correlation (r, 0.31, 0.34) for cognitive and non-cognitive items. Students showed improvements in their mean scores for both cognitive (t-test; p > 0.05) and non-cognitive items (t-test; p = 0.000). Mean scores of students were not different statistically from that of staff (p > 0.05). Conclusions Students may adequately act as self-assessors at the beginning of their clinical work in periodontology. Self-assessment may potentially improve the clinical performance. Self-assessment may be nurtured through clear guidelines, educational training strategies, feedback and reflection leading to better evaluative judgement and lifelong learning.

Importance of Eosinophilic Infiltration of the Colonic Mucosa in Ulcerative Colitis Patients who are Refractory to Maintenance Therapy

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely studied. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for clinical background when starting steroid treatment; clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of clinical activity index, Mayo endoscopic subscore, and UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All these scores improved significantly after steroid use (P=0.04, P<0.01, P<0.01, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistant to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.

The value of SPECT/CT imaging of lacrimal glands as a means of assessing the activity of Graves’ orbitopathy

Background: Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include: Clinical Activity Score (CAS), computed tomography (CT), and magnetic resonance imaging (MRI). These approaches are mainly associated with orbital muscles, however, there are not many studies that focus on the lacrimal gland inflammation of GO patients. Objective: The aim of this study is to assess the usefulness of 99mTc-DTPA SPECT/CT in evaluating the lacrimal gland inflammation in Graves orbitopathy, as compared with other methods. Methods: A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical-endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed. Results: The lacrimal glands in patients with GO were significantly larger in all measured dimensions (p < 0.001) on CT scans relative to those in controls. Increased lacrimal gland DTPA uptake ratios (p < 0.001) were displayed in active GO patients compared to controls and were also correlated with TRAb levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients. Conclusions: These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study

BackgroundMatrix metalloproteinase 9 (MMP9) is implicated in protumorigenic processes. Targeting either stromal or epithelial MMP9 reduces the incidence of metastasis. Andecaliximab is a monoclonal antibody that targets MMP9 with high affinity and selectivity. However, no study has examined whether the inhibition of T-cell programmed death 1 (PD-1) in the presence of andecaliximab increases activated lymphocyte infiltration into the tumor, thereby increasing antitumor activity more than that in anti-PD-1 monotherapy. In this study, we assessed the safety, pharmacokinetics (PK), exploratory biomarkers, and preliminary efficacy of andecaliximab as monotherapy and in combination with nivolumab in Japanese patients with advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.MethodsThis phase 1b study comprised four cohorts enrolling Japanese patients with gastric or GEJ adenocarcinoma. This paper concerns cohorts 1 and 4; cohorts 2 and 3 will be reported subsequently. Cohort 1 enrolled patients with human epidermal growth factor receptor 2 (HER2)-negative tumors (n=8) who received andecaliximab monotherapy (800 mg by intravenous infusion every 2 weeks (Q2W)), and cohort 4 enrolled patients irrespective of their HER2 status (n=10) who received 800 mg of andecaliximab in combination with nivolumab Q2W. Safety, dose-limiting toxicities (DLTs), PK, pharmacodynamics, and biomarkers were assessed in both cohorts.ResultsPK of andecaliximab in Japanese patients with gastric or GEJ adenocarcinoma was similar to that reported in non-Japanese patients with advanced solid tumors. Andecaliximab monotherapy and in combination with nivolumab demonstrated no DLTs in cohort 1 and 4, respectively. Toxicities were manageable and well tolerated in both cohorts. The median progression-free survival was 1.4 months (90% CI, 0.5 to 5.4) and 4.6 months (90% CI, 0.9 to not reached) in cohorts 1 and 4, respectively. The objective response rate was 50% (90% CI, 22% to 78%) in cohort 4, and in some patients, the combination therapy was effective regardless of the biomarker status.ConclusionsThe andecaliximab–nivolumab combination demonstrated a manageable safety profile and promising clinical activity in patients with advanced gastric adenocarcinoma.NCT02862535.

The clinical course of a 79-year-old stroke survivor in the setting of a late-onset COVID-19 infection

Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), no specific antiviral drug has been proven effective for the treatment of patients with severe complications. However, a nucleoside prodrug remdesivir (GS-5734) was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with COVID-19. Preclinical data in animal models of coronavirus diseases have demonstrated that early treatment with remdesivir leads to improved survival and decreased lung injury. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of shorter recovery period and higher odds of improved clinical status in patients with COVID-19. Here, the story of a 79-year-old patient, with 11-year-old left hemiparesis, concomitant cardiovascular disease, infected with SARS-CoV-2, and the clinical improvement after administration of remdesivir during his second hospitalization period is reported.

Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency

Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001 ). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02 ), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; p < 0.04 ) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; p = 0.02 ) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02 ) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels ( r = − 0.26 ; p = 0.001 ) and urine proteins (mg/dL) ( r = − 0.39 ; p < 0.01 ). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count ( r = 0.30 ; p < 0.001 ) and negatively correlated with the glomerular filtration rate ( r = − 0.28 ; p = 0.001 ). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins ( r = 0.38 ; p < 0.01 ). The calcidiol deficiency ( OR = 2.27 ; 95% CI = 1.15 -4.49; p < 0.01 ), high calcitriol levels ( T 3 rd , OR = 4.19 , 95% CI = 2.23 -7.90; p < 0.001 ), and a high calcitriol/calcidiol ratio score ( T 3 rd , OR = 5.93 , 95% CI: 3.08-11.5; p < 0.001 ) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.

Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). Conclusions: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.