Showing papers by "London Bridge Hospital published in 2016"

Systemic lupus erythematosus.

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.

The Heart and Arteries

Abstract: There are two areas of the heart which can be affected – the heart valves, and the heart’s own coronary arteries.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

Abstract: SummaryAims The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). Methods The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2–3 years. Independent adjudication was performed on all mortalities and CV outcomes. Results Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Conclusions Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.

Musculoskeletal manifestations of the antiphospholipid syndrome

Abstract: The scope of clinical and laboratory manifestations of the antiphospholipid syndrome (APS) has increased dramatically since its discovery in 1983, where any organ system can be involved. Musculoskeletal complications are consistently reported in APS patients, not only causing morbidity and mortality, but also affecting their quality of life. We reviewed all English papers on APS involvement in the musculoskeletal system using Google Scholar and Pubmed; all reports are summarized in a table in this review. The spectrum of manifestations includes arthralgia/arthritis, avascular necrosis of bone, bone marrow necrosis, complex regional pain syndrome type-1, muscle infarction, non-traumatic fractures, and osteoporosis. Some of these manifestations were reported in good quality studies, some of which showed an association between aPL-positivity and the occurrence of these manifestations, while others were merely described in case reports.

MASTERS-D Study: A Prospective, Multicenter, Pragmatic, Observational, Data-Monitored Trial of Minimally Invasive Fusion to Treat Degenerative Lumbar Disorders, One-Year Follow-Up

Abstract: The objective of the study is to assess effectiveness and safety of minimally invasive lumbar interbody fusion (MILIF) for degenerative lumbar disorders (DLD) in daily surgical practice and follow up with patients for one year after surgery. A prospective, multicenter, pragmatic, monitored, international outcome study in patients with DLD causing back/leg pain was conducted (19 centers). Two hundred fifty-two patients received standard of care available in the centers. Patients were included if they were aged >18 years, required one- or two-level lumbar fusion for DLD, and met the criteria for approved device indications. Primary endpoints: time to first ambulation (TFA) and time to surgery recovery (TSR). Secondary endpoints: patient-reported outcomes (PROs)--back and leg pain (visual analog scale), disability (Oswestry Disability Index (ODI)), health status (EQ-5D), fusion rates, reoperation rates, change in pain medication, rehabilitation, return to work, patient satisfaction, and adverse events (AEs). Experienced surgeons (≥30 surgeries pre-study) treated patients with DLD by one- or two-level MILIF and patients were evaluated for one year (NCT01143324). At one year, 92% (233/252) of patients remained in the study. Primary outcomes: TFA, 1.3 ±0.5 days and TSR, 3.2 ±2.0 days. Secondary outcomes: Most patients (83.3%) received one level MILIF; one (two-level) MILIF mean surgery duration, 128 (182) min; fluoroscopy time, 115 (154) sec; blood loss, 164 (233) mL; at one year statistically significant (P<.0001) and clinically meaningful changes from baseline were reported in all PROs--reduced back pain (2.9 ±2.5 vs. 6.2 ±2.3 at intake), reduced leg pain (2.2 ±2.6 vs. 5.9 ±2.8), and ODI (22.4% ± 18.6 vs. 45.3% ± 15.3), as well as health-related quality of life (EQ-5D index: 0.71 ±0.28 vs. 0.34 ±0.32). More of the professional workers were working at one year than those prior to surgery (70.3% vs. 55.2%). Three AEs and one serious AE were considered procedure-related; there were no deep site infections or deaths. This is the first study evaluating MILIF for treatment of DLD in daily clinical practice. Clinically significant improvements were observed in all endpoints. Short-term post-surgery improvements (four weeks) were maintained through one year with minimal complications. Our results suggest that MILIF has good-to-excellent outcomes for the treatment of DLD in a broad patient population under different clinical conditions and healthcare delivery systems.

Genetic Testing for Rare Cancer: The Wider Issues.

Abstract: Identification of a potential genetic susceptibility to cancer and confirmation of a pathogenic gene mutation raises a number of challenging issues for the patient with cancer, their relatives and the health professionals caring for them. The specific risks and management issues associated with rare cancer types have been addressed in the earlier chapters. This chapter considers the wider issues involved in genetic counselling and genetic testing for a genetic susceptibility to cancer for patients, families and health professionals. The first part of the chapter will present the issues raised by the current practice in genetic counselling and genetic testing for cancer susceptibility. The second part of the chapter will address some of the issues raised by the advances in genetic testing technology and the future opportunities provided by personalised medicine and targeted cancer therapy. Facilitating these developments requires closer integration of genomics into mainstream cancer care, challenging the existing paradigm of genetic medicine, adding additional layers of complexity to the risk assessment and management of cancer and presenting wider issues for patients, families, health professionals and clinical services.

Pregnancy and Fetal Loss

Abstract: For the purpose of clinical definition, pregnancy is divided into two halves, each of 20 weeks. Any pregnancy loss before 20 weeks is classified as abortion and after 20 weeks, when the fetus is well-formed, as fetal loss.

Biological therapies in lupus

Abstract: The use of biologics in lupus has lagged far behind the experience of these agents in rheumatoid arthritis (RA). Lessons learnt in RA (and increasingly in seronegative spondyloarthritis) include the observation that in general the agents now in use are safe, even in the medium to longer term and that they can be used in place of other remedies, if necessary. Furthermore, they can be used in tandem with other biologics, reaching the stage where ‘‘treat to target’’ is now regarded as achievable. Experience in lupus has been less positive. As Nandkumar and colleagues remind us in this special issue of Lupus, ‘‘while several promising treatments have emerged, only one drug, belimumab, has passed regulatory muster’’. Possible reasons for this time lag are many – lupus being less common than RA, the clinical complexity of systemic lupus erythematosus (SLE), the need for additional immunosuppressives in many cases, and of course, the many disappointments in clinical trials along the way. However, there is cause for optimism. Anti-B cell agents, rituximab and now belimumab, despite early trial setbacks, are both successful additions to our lupus treatment repertoire. They promise to profoundly alter lupus clinical practice. One example is the ‘‘no-steroid’’ regime for lupus nephritis being trialed by Liz Lightstone and her team using an initial two pulses of rituximab (and a pulse of methylprednisolone) followed by maintenance mycophenolate mofetil (MMF) and no oral steroids. With deepening understanding of the mechanisms leading to lupus activity, a rapidly increasing number of agents are currently in various stages of trial. Already lessons are being learnt – the heightened risk of infections when biologics are combined with conventional immunosuppressive drugs such as cyclophosphamide and MMF. Plus the (obvious) risk of failure in a drug trial when the background dosage of steroids is high. In this special issue of Lupus, Professor Dan Wallace, whose clinical experience in this area is second to none, has brought together a number of the leaders in the field of new directed therapies in SLE. For me, this special issue brings us an important snapshot of the current status of ‘biologics’ in lupus.