Efficacy of Individualized Homeopathic Medicines in the Treatment of Sciatica Pain: Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: Sciatica is a debilitating condition that causes pain in its distribution or in the lumbosacral nerve root that is connected to it. Although there are claims that homeopathy can reduce sciatica pain, systematic scientific proof is currently lacking. The objective of the trial was to determine whether individualized homeopathic medicines (IHMs) were as effective as identical-looking placebos in treating sciatica pain. Design: This is a double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: The study was conducted at Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Sixty participants with sciatica pain were included in this study. Interventions: Verum (n = 30; IHMs plus concomitant care) versus control (n = 30; placebos plus concomitant care). Outcome measures: Primary-Sciatica Bothersome Index (SBI) and Sciatica Frequency Index (SFI) scores and secondary-Roland Morris Pain and Disability Questionnaire (RMPDQ), Short Form McGill Pain Questionnaire (SF-MPQ), and Oswestry Low Back Pain Questionnaire (OLBPQ) scores: all of them were measured at baseline, and every month, up to 3 months. Results: Intention-to-treat sample (n = 60) was analyzed. Group differences were examined by two-way (split-half) repeated measure analysis of variance, primarily accounting for between groups and time interactions, and additionally, by unpaired t tests comparing the estimates obtained individually every month. The level of significance was set at p < 0.025 and <0.05 two tailed for the primary and secondary outcomes, respectively. Group differences could not achieve significance in SBI (p = 0.044), SFI (p = 0.080), and RMPDQ scores (p = 0.134), but were significant for SF-MPQ (p = 0.007) and OLBPQ (p = 0.036). Gnaphalium polycephalum (n = 6; 10%) was the most frequently prescribed medicine. No harm, serious adverse events, or intercurrent illnesses were recorded in either of the groups. Conclusions: The primary outcome failed to demonstrate evidently that homeopathy was effective beyond placebo, and the trial remained inconclusive. Independent replications are warranted to confirm the findings. Clinical Trial Registration Number: CTRI/2020/10/028617.

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials.

OBJECTIVE: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. METHODS: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. RESULT: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], - 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, - 0.37; 95% CI, - 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. CONCLUSION: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

Metal-induced oxidative stress level in patients with fibromyalgia syndrome and its contribution to the severity of the disease: A correlational study.

BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatological disease characterised by widespread chronic musculoskeletal pain. Metal-induced oxidative stress contributes to the severity of FMS. AIMS: First, this study evaluated the association between plasma levels of toxic heavy metals and essential metals with oxidative stress (OS) markers. Second, the OS markers and metal contents were correlated with the disease severity by assessing the Fibromyalgia Impact Questioner Revised (FIQR) and tender points (TP). METHOD: A total of 105 FMS patients and 105 healthy controls of similar age and sex were recruited. OS parameter such as lipid peroxidation (LPO), protein carbonyl group (PCG), nitric oxide (NO) and essential metals such as zinc (Zn), magnesium (Mg), manganese (Mn), copper (Cu) and toxic heavy metals such as aluminium (Al), arsenic (As), lead (Pb) were estimated. RESULTS: Levels of LPO, PCG, NO (p< 0.001) and Cu, Mn, and Al (p< 0.001), were significantly higher, and Mg (p< 0.001) and Zn (p< 0.001) were significantly lower in patients compared to controls. A positive association was observed between OS parameters, FIQR and TP with Cu, Al and Mn. A significant negative association was observed between Zn and Mg with FIQR, TP and OS parameters. CONCLUSION: Heavy metals such as Al induce OS parameters and decrease the levels of essential trace elements such as Mg and Zn, which may be responsible for the severity of FMS.

Association of Vitamin D Receptor (FokI and BsmI) Gene Polymorphism with Bone Mineral Density and Their Effect on 25-Hydroxyvitamin D Level in North Indian Postmenopausal Women with Osteoporosis.

Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) has been suggested as a candidate gene for osteoporosis. Therefore the present study was aimed to investigate the pattern of allelic variants of VDR gene polymorphism (FokI and BsmI), its influence on vitamin D levels and bone mineral density (BMD) in North Indian postmenopausal women with osteoporosis for possible genetic association. 254 postmenopausal osteoporotic women and 254 postmenopausal non osteoporotic women were included in the study. VDR FokI and BsmI gene polymorphism gene were assessed by the PCR-RFLP method. Serum 25-hydroxyvitamin D was measured by the ELISA. BMD at the L1-L4 lumbar spine, hip, forearm and femoral neck was assessed by dual energy X-ray absorptiometry. The average BMD at spine and hip in postmenopausal women with bb and spine, hip, femoral neck and forearm with ff genotype had significantly low BMD. The frequency of ff genotype and f allele was significantly higher in postmenopausal osteoporotic women when compared with postmenopausal non osteoporotic women. However, no significant association was found between the genotypes and vitamin D levels. Our study reveals that VDR gene FokI and BsmI polymorphism is significantly associated with low bone mineral density. Therefore the ff genotype and f allele of VDR FokI gene may be used as an important risk factor for osteoporosis.

Association of vitamin D receptor gene polymorphism (TaqI and Apa1) with bone mineral density in North Indian postmenopausal women.

Vitamin D receptor (VDR) gene has an important role as a candidate gene for the regulation of bone mass in osteoporosis. However, its association with bone mineral density (BMD) is controversial and has not been established in different ethnic populations. To enhance the understanding of VDR gene polymorphism in the context of BMD, we investigated the plausible genetic association of TaqI and ApaI polymorphism with BMD in North Indian postmenopausal women with osteoporosis.254 osteoporotic women (Age 55.82 ±â€¯6.91) and 254 postmenopausal non osteoporotic women (Age 54.76 ±â€¯6.26) were included in the study. VDR TaqI and ApaI polymorphism were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). BMD was assessed by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L1-L4), hip, forearm and femoral neck. The average BMD with TT genotype was significantly lower at lumbar spine, hip and forearm. The Frequency of TT genotype and t allele was significantly high in osteoporotic women when compared with controls. The average BMD with Aa genotype was higher in ApaI. Furthermore, comparison of frequency distribution of genotype and allele for VDR ApaI between osteoporotic patients and controls did not show any significant difference. Our findings revealed that TaqI gene TT genotype was associated with low BMD in North Indian osteoporotic women. Moreover, TT genotype and t allele associated significantly with osteoporosis in postmenopausal women. Therefore, VDR TaqI gene is an important determinant of risk factor for osteoporosis.

Articular cartilage of knee and first MTP joint are the preferred sites to find double contour sign as an evidence of urate crystal deposition in asymptomatic hyperuricemic individuals.

BACKGROUND/OBJECTIVE: A cross-sectional study to determine the preferred sites of urate crystal deposition in asymptomatic hyperuricemic individuals by ultrasound. METHODS: In two years period twenty four asymptomatic hyperuricemic individuals (serum uric acid ≥7mg/dl) and fifty controls (serum uric acid <7mg/dl) with age more than 18 years were included in this study. Double contour sign was looked for at three articular cartilage sites (first metatarsophalangeal, tibiotalar and femoral condyle) whereas hyperechoic aggregates were looked for at one joint site (radiocarpal joint) and two tendon sites (patellar tendon and triceps tendon). The Chi-square test was used to compare the categorical variables and discrete variables were compared by one way analysis of variance. The p-value<0.05 was considered significant. RESULTS: Eight out of 24 asymptomatic hyperuricemic individuals had ultrasound evidence of urate crystal deposition in first metatarsophalangeal joint area followed by knee joint area which was detected in 6 patients. The detection rate of ultrasound abnormalities in asymptomatic hyperuricemic individuals was 45.8% with two joint area (knee and first metatarsophalangeal) and 50% with six sites assessment. Amongst controls, 16% were found to have these abnormal ultrasound findings. CONCLUSION: The highest predilection of urate crystal deposition in asymptomatic hyperuricemic individuals is the articular cartilage of Knee and first metatarsophalangeal joints. This explain the frequent clinical presentation of arthritis in these joint areas.

Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome.

AIM: In the present study we examined the involvement of oxidative and antioxidative parameters in women with fibromyalgia syndrome (FMS) and also evaluated their correlation with Fibromyalgia Impact Questionnaire Revised (FIQR). METHODS: Oxidative stress was determined by measuring the levels of lipid peroxides (LPO) and protein carbonyls in plasma and antioxidative parameters like catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) in blood lysate in 30 female patients satisfying the American College of Rheumatology (ACR) criteria for FMS and 30 healthy females without FMS. Clinical parameters of FMS were evaluated by FIQR. RESULTS: Activity of enzymes catalase (patients, 41.0 ± 0.94; controls, 57.3 ± 1.58), GR (patients, 24.4 ± 0.77; controls, 28.1 ± 1.13) and GPx (patients, 28.2 ± 0.69; controls, 38.7 ± 0.93) were significantly lower in patients with FMS than in controls, and levels of oxidative stress parameters, LPO (patients, 3.31 ± 0.10; controls, 2.2 ± 0.06) and protein carbonyls (patients, 1.90 ± 0.08; controls, 1.32 ± 0.04) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and FIQR in the patient group. Furthermore, a significant positive correlation was also found between protein carbonyls and FIQR in the patient group than in the control group. CONCLUSION: The present results indicate that women with FMS are exposed to oxidative stress. Moreover, our results also showed that increased oxidative stress parameters are more strongly associated with severity of FMS.

Osteoporosis in Postmenopausal Females with Primary Knee Osteoarthritis in a Vitamin D Deficient Population.

AIM AND OBJECTIVE: To find prevalence of osteoporosis (OP) in postmenopausal females with primary knee osteoarthritis (OA) in India, where there is widespread Vitamin D deficiency (VDD). MATERIAL AND METHODS: 75 postmenopausal women (PMW) fulfilling ACR criteria for Knee OA between 40 - 60 years of age, having OA grade 2 or more as per Kellgren Lawrence grade on anterior- posterior radiograph of the right knee were enrolled. 34 PMW of the same age with normal right knee radiograph were taken as controls. Bone mineral density (BMD) of lumber spine (L1- L4), total hip and left forearm was performed using DXA in all patients and controls. The results were expressed in absolute values (g/cm2) and as per WHO criteria - Osteoporosis: T score < -2.5, Osteopenia: T score between -1 and -2.5. Vitamin D Level was done by ELISA. RESULTS: Body mass index (BMI) of patients was significantly higher than controls (p 0.006). There was no difference in BMD between patients and controls at any site. Forty percent patients and 53% controls had osteopenia (p ns), while 34.6% patients and 41.1% controls had osteoporosis at any site (p ns). When this comparison was made at each site there was no difference between patients and controls. CONCLUSION: Prevalence of osteoporosis in PMW with primary knee OA is similar to that in general population.

Efficacy and safety of golimumab in Indian patients with rheumatoid arthritis: Subgroup data from GO-MORE study.

AIM: To conduct a subgroup analysis of GO-MORE trial Part 1, comparing efficacy and safety of add-on subcutaneous golimumab therapy in rheumatoid arthritis (RA) patients enrolled from and outside India. METHODS: GO-MORE was an open-label, multicenter, prospective trial of add-on golimumab in biologic-naïve RA patients, having active disease despite being on conventional DMARD regimen(s). Part 1 of the study was chosen as the focus of this subgroup analysis because a substantial number of Indian patients (106) were enrolled compared to no Indian patients in Part 2. The primary efficacy outcome was proportion of patients achieving good to moderate DAS28-ESR (Disease Activity Score of 28 joints calculated using erythrocyte sedimentation rate) European League Against Rheumatism (EULAR) response at month 6. RESULTS: Efficacy evaluable population comprised of 105 and 3175 patients from India and outside India, respectively. Safety analysis included 106 patients enrolled from India and 3251 from outside India. A higher proportion of Indian patients had a high disease activity as measured by DAS28 ESR than outside India patients. At month 6, the proportion of Indian and non-Indian patients achieving DAS28-ESR, DAS28 - C-reactive protein, simplified disease activity index (SDAI) remission, and EuroQoL Quality-of-Life Questionnaire (EQ-5D) scores were comparable. Incidence of all adverse events was lower in Indian patients. There were no deaths, cases of tuberculosis or malignancy reported in the patients from India at month 6. CONCLUSIONS: The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients.

Osteocalcin HindIII gene polymorphism not associated with bone mineral density­A study in North Indian postmenopausal osteoporotic women.

Osteoporosis is an important health problem in India owing to the prevalence of vitamin D deficiency across all ages, low level of awareness and higher risk of complications. This disease is characterized by decreased bone mass, bone strength and higher risk of bone fracture. Here, we investigated association between osteocalcin HindIII gene polymorphism and bone mineral density (BMD) in postmenopausal osteoporotic and postmenopausal healthy North Indian women, possibly the first study of this kind in the aforesaid population. We investigated Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) of osteocalcin HindIII in 254 postmenopausal osteoporotic (56.12±7.004 years) and 254 postmenopausal healthy (55.27±5.93 years) North Indian women. BMD at lumbar spine (L1-L4), femoral neck, hip and forearm was measured by dual energy X-ray absorptiometry (DEXA). The results showed no significant correlation between osteocalcin HindIII gene polymorphism and BMD and we conclude that osteocalcin HindIII gene polymorphism may not have major effects on BMD variation in postmenopausal North Indian women.

Evaluating relationship in cytokines level, Fibromyalgia Impact Questionnaire and Body Mass Index in women with Fibromyalgia syndrome.

Cytokines (TNF-α and IL-6) levels are reported to be perturbed in Fibromyalgia syndrome (FMS) patients. Moreover, Body Mass Index (BMI) may also be related to disturbed cytokines level. Therefore, the present study was planned to evaluate the levels of cytokines and to correlate them with BMI and Fibromyalgia Impact Questionnaire Revised (FIQR) in female FMS patients (n= 60) and control group (n= 60). 4 ml of blood samples were taken from both the group of patients and controls to measure the levels of IL-6 and TNF-α . Symptoms of FMS were assessed by FIQR. BMI was calculated by a standard formula of weight in kilograms divided by height in meter square. There were significant differences in BMI levels in FMS patients than in control group. However, no significant association was found between BMI and TNF-α levels, and BMI and IL-6 levels in patient and control groups. However, a significant association was found between FIQR and BMI in patients group. On the basis of the results we conclude that the levels of IL-6 and TNF-alpha are not associated with BMI in FMS patients. Furthermore, patients with higher BMI may fall at the risk of FMS. Therefore, weight management may be an important aspect for treatment of FMS patients.

Sexual dysfunctions and lower urinary tract symptoms in ankylosing spondylitis.

AIM: To determine sexual dysfunctions and urinary symptoms in male ankylosing spondylitis (AS) patients and their association with various disease and patient factors. METHODS: In this prospective case control study conducted at a tertiary care teaching institution, 100 males with AS were compared to 100 controls using International Index of Erectile Function-15 (IIEF), International Prostate Symptom Score (IPSS), Hospital Anxiety and Depression Scale (HADS) and a global question for overall relationship with their partners. Bath AS Functional Index (BASFI), visual analogue scale pain scores, patient global assessment scale and Bath AS Disease Activity Index were also assessed in the AS group. Chi-square test, unpaired t-test and univariate and multivariate binary logistic regression analyses were used to analyze the data. RESULTS: Anxiety, depression, erectile dysfunction (ED), orgasmic dysfunction, intercourse dissatisfaction, overall sexual dissatisfaction, altered overall relationship with partner and lower urinary tract symptoms (LUTS) were significantly (P < 0.05) higher in the AS group as compared to controls. Sexual desire, severe LUTS and bothersome LUTS (quality of life score > 2) were not different (P = 0.76, 0.82 and 0.30 respectively) between the two groups. ED was associated with anxiety, depression, longer disease duration, higher BASFI and higher age in AS patients (P = 0.02, 0.001, 0.02, 0.003 and 0.001 respectively). CONCLUSIONS: AS is associated with higher incidence of sexual dysfunction in male patients. ED is associated with anxiety, depression, longer duration of disease, higher BASFI score and higher age in AS patients.

Problem-focused coping and self-efficacy as correlates of quality of life and severity of fibromyalgia in primary fibromyalgia patients.

OBJECTIVES: Patients with fibromyalgia syndrome (FMS) often experience problems such as poor quality of life (QoL), loss of self-efficacy (SE), inappropriate coping behavior, and chronic widespread pain along with other symptoms. Recent studies have indicated that sense of SE and effective coping strategies (CSs) are the crux on which the management of chronic pain and enrichment of QoL of FMS patients depend. Realizing the importance of this subject for the rehabilitation of the people with FMS, this study aimed at analyzing the correlation between severity of FMS, and QoL, SE, and CSs among the patients of FMS. METHODS: One hundred patients with fibromyalgia (FM) and 100 control subjects were studied. Fibromyalgia Impact Questionnaire-Revised, Quality of Life Scale, Arthritis Self-efficacy Scale, and COPE Scales for CSs were administered to both the groups. RESULTS: Significantly lower SE, poor QoL, and less use of CSs were reported by FM patients (P < 0.01) vis-à-vis healthy people. Problem-focused coping (r = 0.27, P < 0.01) and SE (r = 0.20, P < 0.05) were found to be significantly and positively associated with QoL. Components of Fibromyalgia Impact Questionnaire-Revised, namely, pain, function, and symptoms, were found to be significantly and negatively associated with problem-focused coping (P < 0.05), SE (P < 0.01), and QoL (P < 0.01). CONCLUSIONS: This study confirms that problem-focused CSs and SE are important correlates of QoL and severity of FM in Indian as well as other populations.

Steroids Decrease Prevalence of Positive Tuberculin Skin Test in Rheumatoid Arthritis: Implications on Anti-TNF Therapies.

Tuberculin skin test has been used as an indicator of latent tuberculosis in patients with Rheumatoid Arthritis (RA) before administration of biologicals. Effect of Disease modifying antirheumatic drugs (DMARDs) and steroids on the result of tuberculin skin test (TST) may have important implications in interpretation of results of this test. Objectives. To find the prevalence of positive TST in rheumatoid patients and the effect of standard treatment on the results of TST. Method. In this cross-sectional study two hundred and fifty patients of RA above 18 years of age, classified using 1987 ACR criteria for RA, were enrolled from rheumatology outdoor. Demographics, disease activity, disease duration, and therapy were recorded. All patients underwent TST. Results. Fifty-one (20.4%) patients were found to be tuberculin positive. Tuberculin positivity was not affected by MTX intake but it was significantly low in patients with recent steroid intake as compared to patients who had not taken steroids in last 3 months (3% versus 25%, P = 0.002). Conclusion. Prevalence of tuberculin positivity in patients with RA was found to be low. Results were not affected by methotrexate; however tuberculin skin test results in patients with recent use of steroids are likely to be negative.

Oxidative stress and antioxidative parameters and metal ion content in patients with fibromyalgia syndrome: implications in the pathogenesis of the disease.

Fibromyalgia syndrome (FMS) is characterised by diffuse muscle pain, poor sleep and unrelenting fatigue. Individuals with FMS may also experience headaches, anxiety, depression, poor memory, numbness and tingling in the extremities, cold hands and feet, irritable bowel syndrome and lowered immune function. FMS is a common chronic pain syndrome of unknown etiology and limited treatment options. Previous studies have reported oxidative stress in FMS patients, but the results were inconsistent. Oxidative stress and nitric oxide is involved in FMS pathophysiology, however, it is still not clear whether oxidative stress abnormalities are the cause of FMS. There are several studies indicating oxidative stress in patients with FMS. Oxidant (Malondialdehyde) and antioxidant (Superoxide dismutase) balances were found to be changed in FMS patients. Furthermore, increased free radical levels may be responsible for the development of FMS and free radical-mediated oxidative stress including inflammatory cytokines may also play important roles in its pathogenesis. Moreover, oxidative stress is supposed to be increased in patients with FMS which is related to the severity of FMS symptoms. Therefore, it is important to understand whether the oxidative stress parameters are involved in FMS and what is the relationship between these and antioxidants in FMS patients. In this review we will elucidate the importance of oxidative stress and antioxidants and its possible relationship with FMS. Moreover, as metal toxicity is also reported to be involved in the pathogenesis of FMS, therefore we will also try to establish the role of toxic metals in the pathogenesis of FMS.

Circadian rhythm of serum cortisol in female patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) patients have disturbed sleep patterns which may lead to altered circadian rhythm in serum cortisol secretion. The aim of this study was to assess circadian changes, if any, in serum cortisol levels in female patients with FMS. Cortisol levels were estimated every 6 h during 24 h period; in 40 female patients satisfying ACR criteria for FMS (Age 36.4 ± 9.9), and 40 healthy females without FMS (Age 33.8 ± 11.1). A significant difference in the night time serum cortisol level was observed among the patients and control groups (patients, 12.9 ± 9.7 controls 5.8 ± 3.0; p < 0.01). However, no significant difference was found in serum cortisol levels in patients and control groups in the morning (patients, 28.4 ± 13.2 controls, 27.6 ± 14.5; p > 0.05), afternoon (patients, 14.4 ± 5.6 controls, 14.0 ± 6.6; p > 0.05) and evening hours (patients, 10.9 ± 5.8 controls, 8.9 ± 3.6; p > 0.05). It could be concluded that there is an abnormality in circadian secretion of cortisol in female FMS patients.

Lack of Circadian Pattern of Serum TNF-α and IL-6 in Patients with Fibromyalgia Syndrome.

The present study was designed to test the hypothesis of a circadian variation in circulating levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in women with fibromyalgia syndrome (FMS). Serum levels of IL-6 and TNF-α were measured at 4 h intervals of the day in 50 women with FMS satisfying American College of Rheumatology criteria for FMS (age 36.68 ± 9.89) as well as 50 healthy control women (age 32.82 ± 10.53). Serum TNF-α levels were substantially increased in patients with FMS but showed no circadian variation. In contrast, no difference in the levels of IL-6 was found. Moreover, there was also no circadian variation in both the groups of patients and controls. We conclude that no circadian pattern exists in the circulating levels of serum IL-6 and TNF-α in patients with FMS, although TNF-α levels are found raised in patients with FMS.