Prospective, Multicenter Evaluation of a Polyherbal Supplement alongside Standard-of-Care Treatment for Mild Knee Osteoarthritis

Background. This study aimed to provide clinical information on general and joint performance from individuals taking Tregocel® (containing curcuminoid and extracts of the herbs Harpagophytum procumbens, Boswellia serrata, Apium graveolens, and Zingiber officinale) alongside a standard therapy of symptomatic mild knee osteoarthritis (OA). Methods. This was a multicenter, open-label, prospective, single-arm study, in which Tregocel® was supplemented for 36 weeks. Participants with symptomatic mild knee OA requiring pharmacologic treatment for pain were enrolled. Physical performance (6-minute walk test, WOMAC-pain and functional domain, and heel-thigh distance flexion test), general performance (WOMAC questionnaire), and VAS (Visual Analogue Scale) assessment of knee pain, as well as anti-inflammatory and analgesic medication consumption, were assessed. Results. Between January and April 2019, 107 participants were enrolled and analysed in per protocol population. Mean age was 59.7 (SD 10.8) years, and there were 68.2% women. Mean observation time was 291.1 (SD 7.7) days. Mean increase in 6MWT result observed at the end of the study was 26.0 (SD 30.4) m ( p < 0.001 ). Median VAS score decreased from 60.0 (IQR 50–72) mm at the beginning of the study to 21.0 (IQR 14–30) mm after 36 weeks of product administration ( p < 0.001 ). Regular knee OA medications were taken in 99.1% of subjects at baseline decreasing to 55.1% at the end of the Tregocel® supplementation. Conclusions. During Tregocel® supplementation, participants observed improved functional capacity confirmed in the distance in 6MWT and in the heel-thigh distance flexion test, decreased level of pain, and improved WOMAC scores for all domains.

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AN OPEN-LABEL MULTICENTER OBSERVATIONAL STUDY OF THE EFFICACY, TOLERABILITY, AND SAFETY OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG AMTOLMETIN GUACIL IN PATIENTS WITH KNEE OSTEOARTHRITIS AND DYSPEPSIA

Rheumatology Science and Practice ◽

10.14412/1995-4484-2016-654-659 ◽

2017 ◽

Vol 54 (6) ◽

pp. 654-659 ◽

Cited By ~ 1

Author(s):

E. S. Tsvetkova ◽

L. N. Denisov ◽

A. N. Otteva ◽

A. L. Dubikov ◽

S. P. Yakupova ◽

...

Keyword(s):

Observational Study ◽

Knee Osteoarthritis ◽

Analgesic Effect ◽

Varicose Veins ◽

Health Assessment ◽

Open Label ◽

Serious Adverse Events ◽

Multicenter Observational Study ◽

Knee Oa ◽

Anti Inflammatory

Objective: to investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India) versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA) and signs of dyspepsia.Subjects and methods. The open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%), lower extremity varicose veins (6.4%), and diabetes mellitus (6%). Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA) scale was used to rate dyspepsia.Results and discussion. AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p <0.001) reduction in the WOMAC index (pain and stiffness) and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p < 0.001) and “satisfaction with treatment”. Overall assessment of AMG tolerability was only positive: excellent (33%), good (56%), and satisfactory (11%). There were no serious adverse events (AE). AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients. Conclusion. The findings suggest that AMG offers good prospects for knee OA treatment.

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Comparative study between the effect of neural versus intra-articular dextrose prolotherapy on pain and disability in patients with knee osteoarthritis

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-021-00079-w ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Rehab A. Sallam ◽

Aya A. Abdelkhabir ◽

Adel A. Shabana

Keyword(s):

Knee Osteoarthritis ◽

Womac Pain ◽

Knee Oa ◽

Natural Substances ◽

Group I ◽

Skin Targeting ◽

Vas Scores ◽

Group Ii ◽

Reduced Mobility

Abstract Background Osteoarthritis (OA) is a degenerative disease which presents with joint pain and stiffness and reduced mobility. Knee OA is the commonest cause of disability in adults. Dextrose prolotherapy is a new option used to treat mild-to-moderate knee OA. Neural prolotherapy (NPT) is multiple small injections under the skin targeting painful areas with natural substances. The aim of work was to evaluate and compare neural prolotherapy versus intra-articular dextrose prolotherapy effect on relieving pain and improving disability of knee OA. Results VAS and WOMAC scores improved significantly immediately and at 3 and at 6 months, respectively, in group I compared with group II (P < 0.001). The decrease in VAS scores and all the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in group I along the follow-up period in comparison with the baseline scores was statistically significant (P < 0.001). In group II, only WOMAC pain and stiffness scores improved significantly. ROM showed insignificant increase in both groups at 3 and 6 months assessment. On follow-up, range of motion increased in both groups and reached significance in group I (P = .002). Conclusion Dextrose prolotherapy both intra-articular and periarticular (neural) is a very effective and cheap therapy for knee OA with good patient selection. Neural prolotherapy significantly relieves pain and improves function in patients with knee osteoarthritis when compared with intra-articular prolotherapy thus avoiding hazards of intra-articular knee injections.

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T2 mapping evaluation of changes in cartilage matrix after PRP and HA injection therapy in knee osteoarthritis: a prospective, randomized, double blind, placebo controlled study

10.21203/rs.3.rs-36493/v1 ◽

2020 ◽

Author(s):

Matjaz Vogrin ◽

Jakob Naranda ◽

Mario Gorenjak ◽

Tomaz Bajec ◽

Domen Mongus ◽

...

Keyword(s):

Placebo Group ◽

Knee Osteoarthritis ◽

Pain Score ◽

T2 Mapping ◽

Womac Score ◽

Controlled Study ◽

Womac Pain ◽

Womac Pain Score ◽

Knee Oa

Abstract BackgroundIn this study we focused on evaluating the effect of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) on the qualitative and quantitative properties of the articular cartilage in patients with knee osteoarthritis (OA).MethodsWe evaluated 264 patients undergoing treatment of moderate knee OA. Patients aged between 40 and 70 years were included with articular K-L stage ≤ 2. Patients were randomized into three groups and treated with three doses of intra-articular PRP, HA, or placebo injection. Patients were evaluated clinically and by using T2 mapping.ResultsBoth PRP (619.05 ± 243 ms; p = 2.7 × 10− 5) and HA (637.12 ± 273 ms; p = 1.×10− 4) group showed statistically significant lower post-application T2 relaxation times in comparison to the placebo group (859.80 ± 406 ms).Cartilage thickness increased significantly after PRP (2.41±0.87 vs. 2.58±0.97 mm, p=0.033) and HA (2.28±0.81 vs. 2.80±1.00 mm, p=1.8×10) applications. There was a significant decrease in WOMAC pain score by 30% (p=0,001) and the overall WOMAC score by 27 p=1.9×10-4%) in PRP group. The decrease in WOMAC pain score and the overall WOMAC score in the placebo group was similar to the results observed in the PRP group. In the HA group a significant decrease in WOMAC pain score by 14% (p=0,005) was observed only at the first follow-up, whereas no difference was observed at the second follow-up. ConclusionsT2 mapping of cartilage tissue may aid to monitor its properties after the intra-articular therapies in knee OA. However, there is a discrepancy between clinical findings and the results of T2 mapping, suggesting questionable grounds for applying intra-articular therapy.

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Comparison Of Diacerein-Ginger With Diacerein Alone In Treating Knee Osteoarthritis

Journal of Bahria University Medical and Dental College ◽

10.51985/jbumdc2019096 ◽

2019 ◽

Vol 09 (04) ◽

pp. 308-311

Author(s):

Mehtab Munir ◽

Shahid Mustafa Memon ◽

Sajid Abbas Jaffri ◽

Khalid Mustafa Memon

Keyword(s):

Knee Osteoarthritis ◽

P Value ◽

Womac Pain ◽

Test Results ◽

Knee Oa ◽

Significant Difference ◽

Group A ◽

Insignificant Difference ◽

Group B ◽

Pain At Rest

Objective: To compare clinical efficacy of diacerein-ginger with diacerein alone in treating knee osteoarthritis. Duration and place of study: It was a randomized clinical trial conducted from 21st September 2018 to 31stMarch 2019, in medical OPD of a private hospital in Karachi. Methodology: 60 diagnosed patients of knee osteoarthritis were included in this study. Male and female patients 50 years of age, fulfilling the inclusion criteria and after written informed consent experienced a wash-out period of 72 hours. These patients were systematically randomized into 2 groups each having 30 members. Group A received capsule Diacerein 50mg + capsule Ginger 550 mg twice daily and group B received capsule Diacerein 50mg twice daily, for 12 weeks. Parameters checked at 0, 6 and 12 weeks were: Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, pain at rest and movement (Visual Analogue Scale). Comparison of the two groups was done by independent t-test. Results: Among 60 patients; 20 (33.33 %) were males and 40 (66.66%) were females. 4 patients in group A and 4 in B, dropped out during the study. Comparison of group A with group B in WOMAC and pain (at rest and movement) scores showed insignificant difference at day 0 before prescription of the drugs. However comparison showed highly significant difference (P-value < 0.001) between the two groups in WOMAC, pain at rest and movement scores at the end of 6th and 12th weeks of intervention. Conclusion: Diacerein-Ginger is clinically more efficacious for management of knee OA than Diacerein alone

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Effect of Nucart VG (Boswellia serrata in combination with veg glucosamine sulphate) in comparison with glucosamine sulphate to improve quality of life of knee osteoarthritis patients: a randomized controlled trial

International Journal of Research in Orthopaedics ◽

10.18203/issn.2455-4510.intjresorthop20213378 ◽

2021 ◽

Vol 7 (5) ◽

pp. 976

Author(s):

Vijay G. Goni ◽

Mukesh Mishra ◽

Sailee Kadam ◽

Sharat S. Gandhi

Keyword(s):

Quality Of Life ◽

Health Status ◽

Knee Osteoarthritis ◽

Controlled Trial ◽

Open Label ◽

Boswellia Serrata ◽

Group Randomized Trial ◽

Glucosamine Sulphate

Background: Boswellia serrata has been proved to be an effective and safe herb for the treatment of osteoarthritis (OA). This study aims at assessing the synergistic effect of this herb with vegetarian glucosamine sulphate, a nutritional supplement, on knee osteoarthritis using quality of life indicators.Methods: This was an open label, parallel group randomized trial of 12-week duration. Sixty-six subjects were equally randomized to two treatment arms: Boswellia serrata extract (600 mg) and glucosamine (750 mg) [Nucart VG]; and glucosamine sulphate (market comparator) 750 mg. Patients were administered 1 tablet twice-a-day post-meal for three months. Efficacy of treatment was measured on primary end-points like EuroQol-5D (EQ-5D) (health status indicator), visual analogue scale (VAS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scale (pain indicators), while safety was measured in terms of vital parameters. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for comparing scores between the two groups.Results: The baseline characteristics of patients between two groups were insignificantly different (p>0.05). In ITT analysis, the health status (EQ-5D score) of patients in Nucart VG group improved significantly than the comparator group at follow up 2 (p=0.037) and showed further improvement at follow up 3 (p=0.012). The pain indicators i.e. VAS and WOMAC scores were significantly lower in Nucart VG group right from follow up 1 till follow up 3 (p<0.05). Similar were the observations during PP analysis.Conclusions: Nucart VG is beneficial for the treatment of mild to moderate knee OA, as inferred from the functional and health status assessment.

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Intra-Articular Hybrid Hyaluronic Acid Injection Treatment in Overweight Patients with Knee Osteoarthritis: A Single-Center, Open-Label, Prospective Study

Applied Sciences ◽

10.3390/app11188711 ◽

2021 ◽

Vol 11 (18) ◽

pp. 8711

Author(s):

Dalila Scaturro ◽

Fabio Vitagliani ◽

Pietro Terrana ◽

Daniele Cuntrera ◽

Vincenzo Falco ◽

...

Keyword(s):

Quality Of Life ◽

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Disease Severity ◽

Prospective Trial ◽

Open Label ◽

Knee Oa ◽

Symptomatic Knee ◽

Significant Difference

Background: A BMI > 25 is the most decisive, albeit modifiable, risk factor for knee osteoarthritis (KOA). This study aimed at assessing the efficacy of intra-articular injections of hybrid hyaluronic acid (HA) complexes (Sinovial® H-L) for the treatment of KOA in overweight patients in terms of disease severity, cardiocirculatory capacity, and quality of life. Materials: In this single-site, open-label, prospective trial, 37 patients with symptomatic knee OA were assessed at baseline and 3 months after ultrasound-guided intra-articular injection of hybrid HA complexes (Sinovial® H-L). Results: Primary variables displaying a statistically significant improvement after treatment were pain (VAS), disease severity (WOMAC), and cardiopulmonary capacity (6 min walk test). Among secondary variables, quality of life (SF-12) improved significantly, as did analgesic intake for pain control. No statistically significant difference was observed in body fat and muscle mass percentage measured by bioelectrical impedance analysis. Conclusions: Intra-articular hybrid HA injections are significantly effective in improving OA-related disease severity, cardiopulmonary function, and analgesic intake. This supports the role of hybrid HA viscosupplementation as a nonpharmacological treatment to relieve pain, reduce disability, improve quality of life, and limit the risk of polypharmacy in overweight patients with knee OA.

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Intra Articular Ozone Modulates Inflammation and Has Anabolic Effect on Knee Osteoarthritis: IL-6 and IGF-1 as Pro-Inflammatory and Anabolic Biomarkers

Processes ◽

10.3390/pr10010138 ◽

2022 ◽

Vol 10 (1) ◽

pp. 138

Author(s):

Marcos E. Fernández-Cuadros ◽

Olga S. Pérez-Moro ◽

María J. Albaladejo-Florín ◽

María M. Tobar-Izquierdo ◽

Amelia Magaña-Sánchez ◽

...

Keyword(s):

Uric Acid ◽

Knee Osteoarthritis ◽

Real World ◽

Secondary Outcome ◽

Womac Pain ◽

Anabolic Effect ◽

Obese Patients ◽

Knee Oa ◽

Before And After ◽

Anti Inflammatory

Objectives: (1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world rehabilitation setting; (2) to differentiate Ozone effect in diabetic (DM)/obese and non-DM/non-obese patients; (3) to evaluate clinical effectiveness by visual analog scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study ran from January 2018 to September 2021. Inclusion criteria: (a) patients 18 years or older; (b) with knee OA KL 2° or more; (c) biochemical analysis before-and-after treatment; (d) pain more than 3 on VAS. Exclusion Criteria: (a) previous knee surgery; (b) favism; (c) pregnancy; (d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: (a) IL-6; (b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: (a) CRP, (b) ESR, (c) uric acid, (d) VAS pain, (e) WOMAC pain, function and stiffness. Ozone protocol consisted of four sessions (once a week) of an intra-articular infiltration of 20 mL (20 µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by a Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.70 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only non-DM/non-obese knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p < 0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in a real world rehabilitation setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone tends to downregulate pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

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Depression in patients with knee osteoarthritis: risk factors and associations with joint symptoms

10.21203/rs.3.rs-31807/v2 ◽

2020 ◽

Author(s):

Shuang Zheng ◽

Liudan Tu ◽

Flavia Cicuttini ◽

Zhaohua Zhu ◽

Weiyu Han ◽

...

Keyword(s):

Risk Factors ◽

Knee Joint ◽

Knee Osteoarthritis ◽

Controlled Trial ◽

Womac Pain ◽

Knee Oa ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee ◽

Joint Symptoms ◽

Patient Health

Abstract Background:To describe demographic and clinical factors associated with the prevalence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods:413 participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.2 ± 7.0 year, 50.4% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results: The prevalence and incidence of depression was 25.4% and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher prevalence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the prevalence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA.Trial registration: ClinicalTrials.gov identifier: NCT01176344Anzctr.org.au identifier: ACTRN12610000495022

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Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial

Journal of International Medical Research ◽

10.1177/0300060517723182 ◽

2017 ◽

Vol 46 (1) ◽

pp. 326-334 ◽

Cited By ~ 17

Author(s):

Jianping Wang

Keyword(s):

Knee Osteoarthritis ◽

Global Assessment ◽

Controlled Trial ◽

Womac Pain ◽

Physician Global Assessment ◽

Efficacy And Safety ◽

Open Label ◽

Womac Pain Score ◽

Physical Function Score ◽

Pain Visual Analog Scale

Objective To evaluate the efficacy and safety of adalimumab (ADA) versus hyaluronic acid (HA) by intra-articular injection for moderate to severe knee osteoarthritis. Methods Fifty-six consecutive patients with moderate to severe knee osteoarthritis were randomly allocated to either the ADA group or HA group. On day 0, patients in the ADA group received 10 mg of ADA by intra-articular injection, while those in the HA group received 25 mg of HA. All patients received celecoxib at 200 mg/day for 4 weeks. The pain visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Patient Global Assessment (PGA), and Physician Global Assessment (PhGA) scores were assessed. Results At baseline, the pain VAS, WOMAC, PGA, and PhGA scores were similar between the two groups. The decrease in the pain VAS score, WOMAC pain score, WOMAC physical function score, and WOMAC total score from baseline to week 4 were greater in the ADA than HA group. A greater decrease in the PGA and PhGA scores from baseline to week 4 was noted in the ADA than HA group. No difference in adverse events was observed between the two groups. Conclusion ADA by intra-articular injection was effective and tolerated for moderate to severe knee osteoarthritis.

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High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03729-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Charles D. Hummer ◽

Felix Angst ◽

Wilson Ngai ◽

Craig Whittington ◽

Sophie S. Yoon ◽

...

Keyword(s):

Molecular Weight ◽

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Treated Patient ◽

Meta Analysis ◽

Credible Interval ◽

Pain Scale ◽

Womac Pain ◽

Knee Oa ◽

Mean Differences

Abstract Background The 2013 American Academy of Orthopaedic Surgeons (AAOS) guidelines made strong recommendations against intraarticular hyaluronic acid (IAHA) for patients with knee osteoarthritis (OA), as evidence supporting improvements in pain did not meet the minimal clinically important improvement (MCII) threshold. However, there may be important distinctions based on IAHA molecular weight (MW). Hence our objective was to evaluate the efficacy of IAHAs in knee OA based on molecular weight. Methods Randomized controlled trials were searched within MEDLINE, Embase, and CENTRAL and selected based on AAOS criteria. A pain measure hierarchy and longest follow-up were used to select one effect size from each trial. Mean differences between interventions were converted to standardized mean differences (SMDs) and incorporated into a random-effects Bayesian network meta-analysis. High MW (HMW) was defined as ≥6000 kDa, and low MW (LMW) as < 750 kDa. Results HMW IAHA was associated with a statistically significant and possibly clinically significant improvement in pain (SMD − 0.57 (95% credible interval [Crl]: − 1.04, − 0.11), exceeding the − 0.50 MCII threshold. LMW IAHA had a lesser, non-significant improvement (− 0.23, 95% Crl: − 0.67, 0.20). Back-transforming SMDs to the WOMAC pain scale indicated a 14.65 (95% CI: 13.93, 15.62) point improvement over IA placebo, substantially better than the 8.3 AAOS MCII threshold. Conclusions Unlike LMW IAHA, HMW IAHA exceeded the MCII threshold for pain relief, suggesting that improvements can be subjectively perceived by the treated patient. Amalgamation of LMW and HMW may have blurred the benefits of IAHA in the past, leading to negative recommendations. Differentiation according to MW offers refined insight for treatment with IAHA.

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