Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

Non-pharmacological interventions in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

PURPOSE: To investigate the role of non-pharmaceutical therapies on disease activity in rheumatoid arthritis through systematic review and meta-analysis. METHODS: A review of Pubmed, EMBASE, Web of Science, and the Cochrane Library was performed from inception until March 26, 2019. Only randomized controlled trials which assessed oral, non-pharmacological interventions (e.g. diets, vitamins, oils, herbal remedies, fatty acids, supplements, etc.) in adult patients with rheumatoid arthritis, that presented clinically-relevant outcomes (defined as pain, fatigue, disability, joint counts, and/or disease indices) were included in our meta-analysis. Data were analyzed as mean differences between active and placebo and forest plots were performed. Heterogeneity was evaluated using I-squared statistics while funnel plots and Cochrane's risk of bias assessment evaluated bias. RESULTS: 8170 articles were identified in the search and 51 were RCTs were included. The mean difference in DAS28 was significantly improved in experimental group treated with diet (-0.46 [-0.91, -0.02], p = 0.04), zinc sulfate, copper sulphate, selenium, potassium, lipoic acid, turmeric, pomegranate extract, chamomile, and cranberry extract supplements (-0.77 [-1.17, -0.38], p < 0.001), A, B6, C, D, E, and K vitamins (-0.52 [-0.74, -0.29], p < 0.001), and fatty acids (-0.19 [-0.36, -0.01], p = 0.03). Other clinical metrics such as SJC, TJC, HAQ, SDAI, ACR20, and self-reported pain were decreased in the treatment groups. There was significant reporting bias in the studies. CONCLUSION: Some non-pharmacological therapies may modestly improve some clinical outcomes in patients with rheumatoid arthritis. Many identified studies lacked full reporting. Further clinical trials that are well-designed, adequately powered, and sufficiently report ACR improvement criteria or EULAR response criteria outcomes are needed to confirm the efficacy of these therapies.

Osteoporosis and osteonecrosis in systemic lupus erythematosus / Osteoporosis y osteonecrosis en el lupus eritematoso sistémico

ABSTRACT Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines.

RESUMEN La mitad de los pacientes con lupus eritematoso sistémico (LES) tendrá una densidad ósea disminuida, y más de uno de cada 10 desarrollará osteoporosis (OP) prematuramente. Son múltiples los factores de riesgo que se han relacionado con la pérdida de la masa ósea, pero solo unos pocos son modificables, tales como la ingesta de niveles adecuados de vitamina D y de calcio, ejercicio con pesas, controlar la actividad del LES, y limitar el uso de glucocorticoides (GC). También se ha encontrado una estrecha relación entre el uso de GC y osteonecrosis o a necrosis avascular (NAV). Las principales consecuencias de la OP y de la NAV son fracturas, que generan una limitación funcional importante, pérdida de la calidad de vida y aumento de la morbilidad. Las fracturas por osteoporosis se pueden reducir mediante un tamizaje adecuado con densitometría ósea y administrando tratamiento profiláctico cuando se requieren GC de largo plazo o a altas dosis. No existe un tamizaje formal para la NAV, pero su diagnóstico se realiza con imágenes (radiografía, gammagrafía ósea o imágenes avanzadas cuando corresponda). El apuntar a la menor dosis posible de GC, en combinación con inmunosupresión, además de la temprana identificación de los síntomas, ayudará a prevenir otras complicaciones. El presente artículo es una revisión práctica de la epidemiología, la fisiopatología y el manejo de la OP y la NAV en pacientes con LES, en función de la evidencia y de las guías disponibles.

Calcium channel blockers for primary and secondary Raynaud's phenomenon.

BACKGROUND: Raynaud's phenomenon is a vasospastic disease characterized by digital pallor, cyanosis, and extremity pain. Primary Raynaud's phenomenon is not associated with underlying disease, but secondary Raynaud's phenomenon is associated with connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. Calcium channel blockers promote vasodilation and are commonly used when drug treatment for Raynaud's phenomenon is required. OBJECTIVES: To assess the benefits and harms of calcium channel blockers (CCBs) versus placebo for treatment of individuals with Raynaud's phenomenon with respect to Raynaud's type (primary vs secondary) and type and dose of CCBs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (May 19, 2017), MEDLINE (1946 to May 19, 2017), Embase (1947 to May 19, 2017), clinicaltrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Portal. We applied no language restrictions. We also searched bibliographies of retrieved articles and contacted key experts for additional and unpublished data. SELECTION CRITERIA: All randomized controlled trials (RCTs) comparing calcium channel blockers versus placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed search results and risk of bias and extracted trial data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: This review contains 38 RCTs (33 cross-over RCTs) with an average duration of 7.4 weeks and 982 participants; however, not all trials reported all outcomes of interest. Nine of the identified trials studied patients with primary Raynaud's phenomenon (N = 365), five studied patients with secondary Raynaud's phenomenon (N = 63), and the rest examined a mixture of patients with primary and secondary Raynaud's phenomenon (N = 554). The most frequently encountered risk of bias types were incomplete outcome data and poor reporting of randomization and allocation methods.When researchers considered both primary and secondary Raynaud's phenomenon, evidence of moderate quality (downgraded for inconsistency) from 23 trials with 528 participants indicates that calcium channel blockers (CCBs) were superior to placebo in reducing the frequency of attacks. CCBs reduced the average number of attacks per week by six ( weighted mean difference (WMD) -6.13, 95% confidence interval (CI) -6.60 to - 5.67; I² = 98%) compared with 13.7 attacks per week with placebo. When review authors excluded Kahan 1985C, a trial showing a very large reduction in the frequency of attacks, data showed that CCBs reduced attack frequency by 2.93 per week (95% CI -3.44 to -2.43; I² = 77%).Low-quality evidence (downgraded for imprecision and inconsistency) from six trials with 69 participants suggests that the average duration of attacks did not differ in a statistically significant or clinically meaningful way between CCBs and placebo (WMD -1.67 minutes, 95% CI -3.29 to 0); this is equivalent to a -9% difference (95% CI -18% to 0%).Moderate-quality evidence (downgraded for inconsistency) based on 16 trials and 415 participants showed that CCBs reduced attack severity by 0.62 cm (95% CI -0.72 to - 0.51) on a 10-cm visual analogue scale (lower scores indicate less severity); this was equivalent to absolute and relative percent reductions of 6% (95% CI -11% to -8%) and 9% (95% CI -11% to -8%), respectively, which may not be clinically meaningful.Improvement in Raynaud's pain (low-quality evidence; downgraded for imprecision and inconsistency) and in disability as measured by a patient global assessment (moderate-quality evidence; downgraded for imprecision) favored CCBs (pain: WMD -1.47 cm, 95% CI -2.21 to -0.74; patient global: WMD -0.37 cm, 95% CI -0.73 to 0, when assessed on a 0 to 10 cm visual analogue scale, with lower scores indicating less pain and less disability). However, these effect estimates were likely underpowered, as they were based on limited numbers of participants, respectively, 62 and 92. For pain assessment, absolute and relative percent improvements were 15% (95% -22% to -7%) and 47% (95% CI -71% to -24%), respectively. For patient global assessment, absolute and relative percent improvements were 4% (95% CI -7% to 0%) and 9% (95% CI -19% to 0%), respectively.Subgroup analyses by Raynaud's type, CCB class, and CCB dose suggest that dihydropyridine CCBs in higher doses may be more effective for primary Raynaud's than for secondary Raynaud's, and CCBs likely have a greater effect in primary than in secondary Raynaud's. However, differences were small and were not found for all outcomes. Dihydropyridine CCBs were studied as they are the subgroup of CCBs that are not cardioselective and are traditionally used in RP treatment whereas other CCBs such as verapamil are not routinely used and diltiazem is not used as first line subtype of CCBs. Most trial data pertained to nifedipine.Withdrawals from studies due to adverse effects were inconclusive owing to a wide CI (risk ratio [RR] 1.30, 95% CI 0.51 to 3.33) from two parallel studies with 63 participants (low-quality evidence downgraded owing to imprecision and a high attrition rate); absolute and relative percent differences in withdrawals were 6% (95% CI -14% to 26%) and 30% (95% CI -49% to 233%), respectively. In cross-over trials, although a meta-analysis was not performed, withdrawals were more common with CCBs than with placebo. The most common side effects were headache, dizziness, nausea, palpitations, and ankle edema. However, in all trials, no serious adverse events (death or hospitalization) were reported. AUTHORS' CONCLUSIONS: Randomized controlled trials with evidence of low to moderate quality showed that CCBs (especially the dihydropyridine class) may be useful in reducing the frequency, duration, severity of attacks, pain and disability associated with Raynaud's phenomenon. Higher doses may be more effective than lower doses and these CCBs may be more effective in primary RP. Although there were more withdrawals due to adverse events in the treatment groups, no serious adverse events were reported.

The use of micronutrient supplements is not associated with better quality of life and disease activity in Canadian patients with systemic lupus erythematosus.

OBJECTIVE: Associations between the use of micronutrient supplements (MS) and disease activity, quality of life (QOL), and healthcare resource utilization were studied in a Canadian population of patients with systemic lupus erythematosus (SLE). METHODS: QOL was assessed by the Medical Outcomes Study 36-item Short Form. Healthcare resource utilization and disease activity/damage were determined. RESULTS: Of the 259 subjects studied, 53% were MS users and 34% used only calcium/vitamin D. MS users had a higher Systemic Lupus International Collaborating Clinics score and utilized more healthcare resources. Disease activity and QOL were similar between MS users and nonusers. CONCLUSION: MS are frequently used by patients with SLE and are not associated with concomitant benefit on QOL. MS users utilized more healthcare resources.

The efficacy of complementary and alternative medicine in the treatment of Raynaud's phenomenon: a literature review and meta-analysis.

OBJECTIVE: Conventional treatment for RP is limited due to side effects, and complementary and alternative medicines (CAM) are widely used by the population. Our objective was to find an effective and well-tolerated CAM for the treatment of RP. METHODS: Using MEDLINE, EMBASE and AMED, 20 randomized controlled trials (RCTs) were found and divided into nine treatment subcategories: acupuncture (n = 2 trials), anti-oxidants (n = 2), biofeedback (n = 5), essential fatty acids (n = 3), Ginkgo biloba (n = 1), L-arginine (n = 2), laser (n = 3), glucosaminoglycans (n = 1) and therapeutic gloves (n = 1). Trials in each subcategory were meta-analysed together. RESULTS: Several categories did not have enough trials to do a meta-analysis and most trials were negative, of poor quality and done prior to 1990. Biofeedback was negative for a change in frequency, duration and severity of RP attacks, and actually favoured control (sham biofeedback; P < 0.02). The therapeutic glove favoured active treatment (P < 0.00001). Laser resulted in one less RP attack on average over 2 weeks vs sham [weighted mean difference (WMD) 1.18; 95% CI 1.06, 1.29], and a change in severity of attacks (WMD 1.98; 95% CI 1.57, 2.39; P < 0.05). No significant differences were found in the nutritional supplements that were studied. CONCLUSIONS: There is a need for well-designed trials of CAM in RP. The literature is inconclusive except that biofeedback does not work for RP, therapeutic gloves may improve RP (but results may not be generalizable due to single trial site and no intent-to-treat analysis) and laser may be effective but the improvement may not be clinically relevant.

Are patients with diabetes receiving the same message from dietitians and nurses?

PURPOSE: The purpose of this study was to determine if registered dietitian (RD) and registered nurse (RN) certified diabetes educators (CDEs) provide similar recommendations regarding carbohydrates and dietary supplements to individuals with diabetes. METHODS: A survey was mailed to CDEs in the southern United States. Participants were asked to indicate their recommendations for use of carbohydrates, fiber, artificial sweeteners, and 12 selected dietary and herbal supplements when counseling individuals with diabetes. RESULTS: The survey sample consisted of 366 CDEs: 207 were RNs and 159 were RDs. No statistically significant differences were found between RNs and RDs in typical carbohydrate recommendations for treatment of diabetes. However, RDs were more likely than RNs to make recommendations for fiber intake or use of the glycemic index. A significant difference also was found in the treatment of hypoglycemia: RNs were more likely than RDs to recommend consuming a carbohydrate source with protein to treat hypoglycemia. CONCLUSIONS: Although some differences existed, RD and RN CDEs are making similar overall recommendations in the treatment of individuals with diabetes.

The effect of diet education on the laboratory values and knowledge of hemodialysis patients with hyperphosphatemia.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of 20 to 30 minutes per month of additional diet education on monthly laboratory values (phosphorus, calcium, parathyroid hormone, and calcium/phosphorus product) and knowledge of dietary phosphorus management in hemodialysis patients with hyperphosphatemia. DESIGN: A quasi-experimental design. SETTING: Three outpatient dialysis centers owned by the same corporation in 1 southern state. PATIENTS: Based on a 3-month average serum phosphorus >6.0 mg/dL, 70 patients were selected for participation; 63 dialysis patients completed the study, 32 in the experimental group and 31 in the control group. INTERVENTION: All patients completed a before-and-after knowledge test and had monthly blood samples drawn. Each month, the same registered dietitian provided the routine laboratory results review with control group. The experimental group received the routine laboratory review plus 20 to 30 minutes of additional diet education specifically targeting phosphorus. Main outcome measures Before-and-after knowledge test results and baseline and final serum calcium, phosphorus, parathyroid hormone, and calcium/phosphorus product levels. RESULTS: At baseline, there were no significant differences in any of the laboratory values, but the knowledge level of the experimental group was greater (P <.05) After 6 months, gains in knowledge were significantly higher in the intervention group, and the serum phosphorus and calcium/phosphorus product levels were significantly lower (P <.01) than in the control group. CONCLUSION: Based on this research, those patients who received extra education monthly showed positive changes, which may be beneficial in reducing hyperphosphatemia.