Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

BACKGROUND: Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. OBJECTIVE: To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. DESIGN: 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). SETTING: 7 secondary and tertiary care pain management centers in the United Kingdom. PARTICIPANTS: 111 patients with moderate or severe CRPS of 1 to 5 years' duration. INTERVENTION: IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. MEASUREMENTS: The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. RESULTS: The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. LIMITATIONS: Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects. CONCLUSION: Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration. PRIMARY FUNDING SOURCE: Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Program, Pain Relief Foundation, and Biotest United Kingdom.

Implementing a three-hourly feeding schedule in stable preterm infants to decrease maternal fatigue.

BACKGROUND: A three-hourly feeding schedule has been shown to be as safe as a two-hourly schedule in preterm neonates. It saves nursing time and may be less tiring for the mothers. However, tradition and apprehensions have prevented its wider acceptance. We used a quality improvement approach to implement a three-hourly feeding schedule in stable preterm infants >32 weeks postmenstrual age (PMA) in our unit through a series of plan-do-study-act (PDSA) cycles. METHODS: All preterm neonates >32 weeks PMA, who were on full enteral feeds and without any respiratory support were eligible. The key quantitative outcome was maternal fatigue score. Safety was assessed in terms of episodes of hypoglycaemia and feed intolerance. Qualitative experiences from nursing staff were captured. The volume of expressed breastmilk and requirement of formula feeds were also recorded. After recording baseline data on a two-hourly feeding schedule, four PDSA cycles were sequentially completed over 21 weeks. The results of each PDSA cycle informed the change strategy for the next cycle. RESULTS: In the baseline phase, five neonates on a two-hourly schedule were studied. In PDSA cycles I, II, III and IV, a cumulative of 122 neonates were studied on a three-hourly schedule. There was a significant decrease in median maternal fatigue score (13 (IQR 8-23) to 3 (IQR 1-6); p=0.01)). Only one neonate had feed intolerance, while two had mild asymptomatic transient hypoglycaemia. Six (5%) neonates were shifted to two-hourly feeds temporarily due to transient reasons. Nursing staff felt mothers could devote more time to Kangaroo mother care. The volume of expressed breastmilk and requirement of formula feeds were not different from the three-hourly schedule. CONCLUSIONS: It was possible to change the traditional two-hourly feeding schedule to three-hourly in stable preterm infants using a quality improvement approach, while objectively documenting its safety and benefits.

A prospective study of cutaneous manifestations of spinal dysraphism from India.

Recognition of cutaneous markers of spinal dysraphism is important to prevent the morbidity associated with underlying spinal anomalies. To investigate the frequency and type of cutaneous stigmata in different forms of spinal dysraphism and to assess the role of ultrasonography and/or magnetic resonance imaging in diagnosing spinal dysraphism at two pediatric dermatology tertiary care centers. Over a 4-year period, all pediatric patients presenting to the dermatology clinic with dorsal midline cutaneous stigmata were evaluated clinically and with imaging studies (radiography, ultrasonographic examination and magnetic resonance imaging/Doppler). Surgical interventions were planned in conjunction with neurosurgery and orthopedic specialists. On examination, 245 (4.2%) had 285 cutaneous stigmata. Of the 180 patients evaluated with radiography, ultrasonographic examination and magnetic resonance imaging, 50 patients (28%) had spinal dysraphism (with 64 cutaneous stigmata). The most common stigmata associated with occult spinal dysraphism were lipoma (10) and dimples (12) and in open spinal dysraphism lipomeningomyelocoele (10) and meningomyelocoele (10). Statistically, lipomeningomyelocoele/myelomeningocoele, atypical dimples and port-wine stains were most associated with spinal dysraphism (p < 0.001). In 80 children less than 6 months of age, radiography with ultrasonographic examination revealed an SD in 16, while magnetic resonance imaging was diagnostic in four cases. Ultrasonographic examination performed fairly well in children less than 6 months and in cases of flat cutaneous stigmata it missed only 5% of cases, but in cases with bulky overlying masses (lipoma, hemangioma) it missed 15% of cases.