Assessing the effectiveness of high frequency repetitive transcranial magnetic stimulation for post-mastectomy pain in breast cancer patients: A randomized controlled trial.

BACKGROUND: Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients. METHODS: We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST). RESULTS: Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078). CONCLUSION: The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients having PMPS, opening new avenues for pain management strategies.

Development and Validation of Total Pain Scale for Evaluation of Total Pain in Cancer Patients.

Objectives: Cancer pain has all the components of total pain such as physical, social, psychological, and spiritual. These components contribute to the overall pain experience in cancer patients. Many instruments have been developed till date to assess the effect of pain in cancer patients but none of the instruments include all components of total pain. In this article, we describe the development and validation of the total pain scale (TPS) for the evaluation of total pain in cancer patients with pain. This study aimed to develop and validate a questionnaire for the evaluation of total pain in cancer patients with pain. Material and Methods: This study included a review of existing pain questionnaires for cancer pain for item pool generation. Items were generated in the Hindi language by six stakeholders to create 23 items to develop TPS. TPS was applied to 300 Hindi-speaking cancer patients. Bivariate correlation was used to reduce the number of items as well as construction of the domain followed by factor analysis to finalise TPS. Confirmatory factor analysis (CFA) was performed for testing the validity and reliability of TPS. Results: TPS is an 18-item scale composed of four domains (physical, social, spiritual and psychological domain). The internal consistency of TPS and its subscales was found to be very good (a = 0.84-0.88). CFA and structural equation modeling Goodness of fit has confirmed that model 4 is the best fit as it yielded a lesser root-mean-squared error of approximation value of 0.062 and a greater comparative fit index, Tucker-Lewis index value of 0.944. The convergent and divergent validity of TPS and its domain was good. Conclusion: This study reports TPS to be a brief (18-item), valid, and reliable questionnaire in the Hindi language for assessment of all components of total pain in cancer patients with pain.

Non-Invasive Objective Markers to Measure Pain: A Direction to Develop a Pain Device - A Narrative Review.

Objective: To review the literature regarding non-invasive objective measurements of pain. Measuring pain is of uttermost importance, but it can be an inconvenient task, especially in terms of the interpretation of patient's information. Reiterating, there is no "standard" that provides the physician with a method to objectively quantify this problem of patient's pain. For assessing the pain, physician relies solely on unidimensional assessment tools or questionnaire-based pain assessment. Although pain is a subjective experience of the patient, but there is a need to measure pain sometimes in the individuals who cannot communicate their quality and severity of pain. Material and Methods: The articles from PubMed and Google Scholar without any year and age limit were searched in the current narrative review. A total of 16 markers were searched and their relation to pain was studied. Results: Studies have shown that these markers change in relation to pain and it can be considered a valuable tool for pain measurement but there are multiple factors like psychological and emotional factors which affect these markers. Conclusion: There is lack of evidence to show which marker can be used for measuring pain accurately. This narrative review is an attempt to look into the various pain-related markers that can be used and it calls for further studies including clinical trials with different diseases and taking into accounts different factors affecting pain to give an accurate measurement of pain.

Homeopathy as an Adjuvant to Standard Care in Moderate and Severe Cases of COVID-19: A Single-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVES: This study aimed to evaluate whether individualized homeopathic medicines have a greater adjunctive effect than adjunctive placebos in the treatment of moderate and severe cases of coronavirus disease 2019 (COVID-19). METHODS: The study was a randomized, single-blind, prospective, placebo-controlled clinical trial set in the clinical context of standard care. INTERVENTION: Patients of either sex, admitted in a tertiary care hospital, suffering from moderate or severe COVID-19 and above 18 years of age were included. In total, 150 patients were recruited and then randomly divided into two groups to receive either individualized homeopathic medicines or placebos, in addition to the standard treatment of COVID-19. OUTCOME MEASURES: The primary outcome was time taken to achieve RT-PCR-confirmed virus clearance for COVID-19. Secondary outcomes were changes in the Clinical Ordinal Outcomes Scale (COOS) of the World Health Organization, the patient-reported MYMOP2 scale, and several biochemical parameters. Parametric data were analyzed using unpaired t-test. Non-parametric data were analyzed using the Wilcoxon signed rank test. Categorical data were analyzed using Chi-square test. RESULTS: In total, 72 participants of the add-on homeopathy (AoH) group showed conversion of RT-PCR status to negative, in an average time of 7.53 ± 4.76 days (mean ± SD), as compared with 11.65 ± 9.54 days in the add-on placebo (AoP) group (p = 0.001). The mean COOS score decreased from 4.26 ± 0.44 to 3.64 ± 1.50 and from 4.3 ± 0.46 to 4.07 ± 1.8 in the AoH and AoP groups respectively (p = 0.130). The mortality rate for the AoH group was 9.7% compared with 17.3% in the AoP group. The MYMOP2 scores between the two groups differed significantly (p = 0.001), in favor of AoH. Inter-group differences in the pre- and post- mean values of C-reactive protein, fibrinogen, total leukocyte count, platelet count and alkaline phosphatase were each found to be statistically significant (p <0.05), favoring AoH; six other biochemical parameters showed no statistically significant differences. CONCLUSION: The study suggests homeopathy may be an effective adjunct to standard care for treating moderate and severe COVID-19 patients. More rigorous, including double-blinded, studies should be performed to confirm or refute these initial findings.

Prevalence of Monoclonal Gammopathy of Undetermined Significance in India-A Hospital-based Study.

BACKGROUND: We sought to determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a hospital-based cohort in India. PATIENTS AND METHODS: From March 2015 to May 2015, 3429 patients (age range, 40-88 years) were enrolled in the present study. Of the 3429 enrolled patients, 2354 (68.6%) were men and 1075 (31.4%) were women. Serum samples were collected from all patients and analyzed using serum protein electrophoresis (SPEP). The positive SPEP samples were subjected to immunofixation. The patients with positive results for both SPEP and immunofixation were registered in the oncology department and investigated further for plasma cell dyscrasias. RESULTS: Of the 3429 study patients, 49 (1.43%) were found to have MGUS, and multiple myeloma was diagnosed in another 6 (0.17%). The prevalence rate of MGUS in patients aged 40 to 49, 50 to 59, 60 to 69, and 70 to 80 years was 0.83%, 1%, 2.62%, and 1.75%, respectively. Of the 49 MGUS patients, 5 (10.2%) were in the high-intermediate risk category using the Mayo Clinic criteria for risk stratification. At 30 months of follow-up, 1 patient in the high-intermediate category had developed multiple myeloma. CONCLUSION: To the best of our knowledge, the present study is the first systematic study on the prevalence of MGUS in an Indian population. The overall prevalence of MGUS was 1.43% in the evaluated Indian cohort, lower than that reported for white and black populations. The incidental detection of 6 subjects with multiple myeloma of 3429 screened subjects in our study was high compared with the reported incidence of multiple myeloma in India of only 1.9 per 100,000 persons. This finding indicates the need to create awareness about myeloma-related symptoms and screening studies in appropriate age groups, at least in the hospital-based setting.

Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma.

The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, ß2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n = 180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p = 0.02) and OS (p < 0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p < 0.05) in PFS and in addition, age> 65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM.

Comedo-ductal carcinoma in situ: A paradoxical role for programmed cell death.

Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in comedo-DCIS and its role in conversion of comedo-DCIS to invasive cancer. Clinical comedo-DCIS excisions and the MCF10DCIS.com human breast cancer model which produces lesions resembling comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody and cell death assessed by Western blotting, Mitocapture and immunohistochemical assays. MCF10DCIS.com cells undergo spontaneous apoptosis in vitro, both in monolayers and multicellular spheroids; it is associated with increased mitochondrial membrane permeability, increase in Bax/Bcl-2 ratio and occurs via caspase-9-dependent p53-independent pathway. This suggests that apoptosis is stromal-independent and that the cells are programmed to undergo apoptosis. Immunostaining with cleaved PARP antibody showed that myoepithelial apoptosis occurs before lesions progress to comedo-DCIS in both clinical comedo-DCIS and in vivo MCF10DCIS.com lesions. Intense staining for MMP-2, MMP-3, MMP-9 and MMP-11 was observed in the stroma and epithelia of solid DCIS lesions prior to conversion to comedo-DCIS in clinical and MCF10DCIS.com lesions. Gelatin zymography showed higher MMP-2 levels in lysates and conditioned media of MCF10DCIS. com cells undergoing apoptosis. These data suggest that signals arising from the outside (microenvironmental) and inside (internal genetic alterations) of the duct act in concert to trigger apoptosis of myoepithelial and luminal epithelial cells. Our findings implicate spontaneous apoptosis in both the etiology and progression of comedo-DCIS. It is possible that spontaneous apoptosis facilitates elimination of cells thus permitting expansion and malignant transformation of cancer cells that are resistant to spontaneous apoptosis.