Significant improvements in pain after a six-week physiotherapist-led exercise and education intervention, in patients with osteoarthritis awaiting arthroplasty, in South Africa: a randomised controlled trial.

BACKGROUND: A major challenge facing those with late stage osteoarthritis is delayed surgery due to waiting lists. In South Africa patients wait years for a hip/knee arthroplasty. Affected patients require effective management to address their pain, especially while awaiting surgery. Existing literature is mostly available from high income countries exploring effects of interventions during short waiting periods. Research is warranted in low income countries where long waiting periods are common. This study explored the effects of a six-week physiotherapist-led exercise and education intervention on pain in this population. METHODS: A randomised controlled trial was performed at two public hospitals in South Africa. Ethical approval and informed consent was obtained. 74 participants from arthroplasty waiting lists were randomly allocated to an intervention (n = 35) or control group (n = 39). The intervention included six physiotherapist-led group-based sessions (two hours/week of education, exercise and relaxation). The control group received usual care. Data collection was conducted by blinded physiotherapists at baseline, week six, 12 and month six. The primary outcome was pain, measured by the Brief Pain Inventory. Additionally, participants completed an open-ended questionnaire at month six, to gain insight regarding the intervention. Analysis was by intention to treat using two-way analysis of variance and post-hoc Tukey comparisons. Answers to subjective questions were analysed according to common themes that emerged. RESULTS: The intervention group had significant improvements compared with the control group with moderate to large effect sizes (ES) on pain severity [week 6: p < 0.01, ES = 0.94, 95 % CI (0.45,1.41), month 6: p = 0.02. ES = 0.74, 95 % CI (0.26,1.2)] and moderate to large effects on pain interference [week 6: p < 0.01, ES = 1.2, 95 % CI (0.70,1.69), week 12: p = 0.04, ES = 0.68, 95 % CI (0.20,1.14), month 6: p < 0.01, ES = 0.98, 95 % CI (0.49,1.45)]. 53 % of participants reported that the intervention improved their pain. CONCLUSIONS: The intervention resulted in sustained significant improvements in pain severity and interference in patients with hip/knee osteoarthritis, awaiting arthroplasty compared with a control group. Additionally, participants' individual feedback supported observed significant improvements in pain. Such an intervention appears to be effective in managing pain in this population and should be incorporated into practice for appropriate patients. Further research is being conducted to explore long term and postoperative outcomes. CLINICAL TRIAL REGISTRATION: Pan African Clinical Trial Registry, PACTR201409000885765 , PACTR201507001186115 .

Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome.

Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation.

Incontinentia pigmenti in a surviving male is accompanied by hypohidrotic ectodermal dysplasia and recurrent infection.

Familial Incontinentia pigmenti (IP) is a rare X-linked dominant condition. The affected cases have characteristic skin lesions, hair, eye, teeth and nail abnormalities and may also have neurological problems. The diagnosis has traditionally been made on clinical grounds. Segregation analysis has suggested that it is lethal in males. Only one liveborn male has been reported who died at one day of age. Female cases of IP survive because of the moderating effects of Lyonization. This child was the affected son of a female with IP. He had a novel phenotype consistent with hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID) but with additional features: he had major problems with hematological disturbances, failure to thrive due to malabsorption, recurrent infections, generalized osteosclerosis and lymphedema of his lower limbs. He also demonstrated some typical features of IP with a generalized reticular skin hyperpigmentation, sparse hair and delayed eruption of teeth. The gene for NEMO (NF-kappa B Essential Modulator) has recently been shown to be mutated in cases of IP. Furthermore, most (80%) of patients possess a recurrent genomic rearrangement that deletes part of the gene resulting in an inactive NEMO protein. In the male case described here, a NEMO stop codon mutation has been identified that has arisen de novo in his affected mother. This mutation is likely to have a less severe effect on NEMO activity and may explain why this child survived for two years and 7 months.