Functional movement disorders (FMDs) are thought to be rare in the elderly. Clinical characteristics of the elderly people who develop FMDs are rarely reported. The objective of this study was to highlight the clinical characteristics of FMD in the elderly and compared these with a cohort of patients with a younger age of onset.The authors performed a retrospective review of the clinical records of patients with FMD who were seen at their center in the last 5 years and had consented to be included in research studies. Patients fulfilling currently accepted diagnostic criteria for FMD as documented, clinically established, or probable were included.Of 151 patients with FMD who were identified and had sufficient information, 21.0% (n=33) had an onset after age 60 years (elderly group). The mean age of onset of FMD was 63.5 years (standard deviation, 5.2 years) in the elderly group and 35.5 years (standard deviation, 12.6 years) in the younger group. Tremor was the most common movement disorder in both groups (elderly group, 33.3%; younger group: 38.9%). Fixed dystonia was not observed in any patient who had an FMD onset after age 60 years. Gait abnormalities were significantly more common in the elderly group (69.7%) than in younger patients (23.5%; P<0.001). Associated psychogenic nonepileptic seizures tended to be more common in elderly patients (18.2%) compared with younger patients (13%; P=0.06).Contrary to common perceptions, FMDs are not uncommon in the elderly, and 1 in 5 patients in the current cohort, onset of FMD occurred after age 60 years. Gait abnormalities and psychogenic nonepileptic seizures may be more common in older patients.
Background In many fields, the choice of a primary endpoint for a trial is not always the ultimate clinical endpoint of interest, but rather some surrogate endpoint believed to be relevant for predicting the effect of the intervention on the clinical endpoint. The classic example of such a field is clinical HIV treatment research, where a variety of primary endpoints are used to evaluate the efficacy of new antiretroviral drugs or new combinations of existing drugs. The choice of endpoint reflects either the goal of therapy as recommended by treatment guidelines (e.g. rapid virological suppression) or the licensing requirements of official drug approval organizations (e.g. time to loss of virological response [TLOVR]).Purpose To review the diversity of endpoints used in recent clinical trials in HIV infection and highlight the methodological issues.Methods We identified articles relating to antiretroviral therapy by searching PubMed and through hand searches of relevant conference abstracts. We restricted the search to randomized controlled trials conducted in HIV-infected adults published/presented from January 2005 until March 2008.Results We identified 28 trials in antiretroviral-naive patients (i.e. patients who were starting antiretroviral therapy for the first time at the time of randomization) and 23 trials in antiretroviral-experienced patients. Most trials were performed for purposes of drug licensing, but others were focused on strategies of using approved drugs. Most trials (40 of 51) used a composite primary endpoint (TLOVR in 13). Of note, 22 of these 40 studies reported that they had used a purely virological efficacy endpoint, but the primary endpoint was actually a composite one due to the way in which missing data and treatment switches were considered as failures.Limitations Examples are restricted to HIV clinical trials.Conclusions Whilst most current HIV clinical trials use composite primary endpoints, there are substantial differences in the components that make up these endpoints. In HIV and other fields where precise definitions are variable, guidelines for standardization of definition and reporting would greatly improve the ability to compare trial results. Clinical Trials 2010; 7: 19-35. http:// ctj.sagepub.com.
Background . Pain is commonly experienced following surgical procedures. Suboptimal management is multifactorial. Objectives . The primary objective was to assess whether patients used a device (Navimed) to self-report pain over and above a normal baseline of observations. Secondary outcome measures included comparison of pain scores and patient use of and feedback on the device. Methods . In a prospective randomized controlled trial, elective gynaecological surgery patients received standard postoperative pain care or standard care plus the Navimed, which allowed them to self-report pain and offered interactive self-help options. Results . 52 female patients, 26 in each of device and standard groups, did not differ in the frequency of nurse-documented pain scores or mean pain scores provided to nurses. The device group additionally reported pain on the device (means 18.50 versus 11.90 pain ratings per day,t(32)=2.75,p<0.001) that was significantly worse than reported to nurses but retrospectively rated significantly less anxiety. 80% of patients found the device useful. Discussion and Conclusion . This study demonstrates that patients used the Navimed to report pain and to help manage it. Further work is required to investigate the difference in pain scores reported and to develop more sophisticated software.
Objective: Little is known about the natural history of the HIV infection in men who have sex with men (MSM) in China. Methods: We compared changes in CD4+ T-cell count and HIV-RNA following seroconversion before starting antiretroviral therapy between MSM in China and in resource-rich countries using data from the Beijing PRIMO cohort and Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE), respectively. Linear mixed models were used to compare rates of CD4 decline (cubic root scale) and changes in HIV-RNA (log10 scale) in the first 3 years following seroconversion. Results: For 131 PRIMO and 3171 CASCADE MSM infected in 2001–2010, estimated CD4+ T-cell count at seroconversion was lower in PRIMO (504 cells/mm3; 95% confidence interval: 463 to 547) compared with CASCADE (554 cells/mm3; 544 to 564). CD4 decline was significantly faster for PRIMO men [−0.59 (−0.72 to −0.47) and − 0.41 (−0.44 to −0.38) cubic root of CD4 count/year for PRIMO and CASCADE, respectively], even after restricting to subtype B (P = 0.01). HIV-RNA at seroconversion was lower in PRIMO compared with CASCADE MSM [difference 0.425 log10/mL (0.249 to 0.603), P < 0.001]. After the first year of seroconversion, PRIMO MSM experienced a faster increase in HIV-RNA [0.830 log10/mL per year; (0.484 to 1.168)] compared with CASCADE MSM [0.018 (− 0.035 to 0.067)] (P < 0.001). Conclusions: CD4 decline and HIV-RNA increase are faster between MSM in China compared with MSM from resource-rich settings. Whether this is due to differences in host immunity or viral characteristics requires further exploration.
Introduction Metastatic spinal cancer is a common condition that may lead to spinal instability, pain and paralysis. In the 1980s, surgery was discouraged because results showed worse neurological outcomes and pain compared with radiotherapy alone. However, with the advent of modern imaging and spinal stabilisation techniques, the role of surgery has regained centre stage, though few studies have assessed quality of life and functional outcomes after surgery. Objective We investigated whether surgery provides sustained improvement in quality of life and pain relief for patients with symptomatic spinal metastases by analysing the largest reported surgical series of patients with epidural spinal metastases. Methods A prospective cohort study of 922 consecutive patients with spinal metastases who underwent surgery, from the Global Spine Tumour Study Group database. Pre- and post-operative EQ-5D quality of life, visual analogue pain score, Karnofsky physical functioning score, complication rates and survival were recorded. Results Quality of life (EQ-5D), VAS pain score and Karnofsky physical functioning score improved rapidly after surgery and these improvements were sustained in those patients who survived up to 2 years after surgery. In specialised spine centres, the technical intra-operative complication rate of surgery was low, however almost a quarter of patients experienced post-operative systemic adverse events. Conclusion Surgical treatment for spinal metastases produces rapid pain relief, maintains ambulation and improves good quality of life. However, as a group, patients with cancer are vulnerable to post-operative systemic complications, hence the importance of appropriate patient selection.
X-linked adrenoleukodystrophy (X-ALD) is a disorder caused by mutations in the ABCD1 gene. The commonest phenotype of X-ALD is adrenomyeloneuropathy (AMN), which is characterised by involvement of the spinal cord and peripheral nerves. The aim of this study was to evaluate bladder and bowel symptoms in men with AMN and female X-ALD carriers.In this cross-sectional study, patients with confirmed mutation of the ABCD1 gene attending a tertiary care service were approached about bladder and bowel complaints and completed the Urinary Symptom Profile (USP), Qualiveen Short Form (SF-Qualiveen), International Prostate Symptom Score (IPSS) and Neurogenic Bowel Dysfunction (NBD) questionnaires. Neurological disability was assessed using the Expanded Disability Status Scale (EDSS).Forty-eight patients participated, 19 males (mean EDSS score (n = 16) 5.0 (95% CI ± 1.03)) and 29 females (mean EDSS score (n = 25) 3.2 (95% CI ± 0.98)). Overactive bladder (OAB) symptoms were reported in both males (100%, n = 19) and females (86.2%, n = 25). There was no significant gender difference in severity of OAB symptoms (P = 0.35) and impact on quality of life (P = 0.13). Furthermore, there was no significant difference in OAB severity when symptoms were compared between female carriers and a cohort of women (n = 17) with spinal cord damage due to multiple sclerosis (P = 0.27). Twenty-one percent (n = 4) of males and 10% (n = 3) of females had moderate to severe bowel dysfunction.Bladder and bowel complaints are common in both men with AMN and female carriers. They have a significant impact on the quality of life yet are under-reported and under-treated. Though having an X-linked pattern of inheritance, female carriers may experience overactive bladder symptoms which are as severe as in male patients and are likely to be neurological in origin.
Surgery for symptomatic spinal metastases aims to improve quality of life, pain, function, and stability. Complications in the postoperative period are not uncommon; therefore, it is important to select appropriate patients who are likely to benefit the greatest from surgery. Previous studies have focused on predicting survival rather than quality of life after surgery.To determine preoperative patient characteristics that predict postoperative quality of life and survival in patients who undergo surgery for spinal metastases.In a prospective cohort study of 922 patients with spinal metastases who underwent surgery, we performed preoperative and postoperative assessment of EuroQol EQ-5D quality of life, visual analog score for pain, Karnofsky physical functioning score, complication rates, and survival.The primary tumor type, number of spinal metastases, and presence of visceral metastases were independent predictors of survival. Predictors of quality of life after surgery included preoperative EQ-5D (P = .002), Frankel score (P < .001), and Karnofsky Performance Status (P < .001).Data from the largest prospective surgical series of patients with symptomatic spinal metastases revealed that tumor type, the number of spinal metastases, and the presence of visceral metastases are the most useful predictors of survival and that quality of life is best predicted by preoperative Karnofsky, Frankel, and EQ-5D scores. The Karnofsky score predicts quality of life and survival and is easy to determine at the bedside, unlike the EQ-5D index. Karnofsky score, tumor type, and spinal and visceral metastases should be considered the 4 most important prognostic variables that influence patient management.
To investigate whether cortical superficial siderosis (cSS) on MRI, especially if disseminated (involving more than 3 sulci), increases the risk of future symptomatic lobar intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).European multicenter cohort study of 118 patients with CAA (104 with baseline symptomatic lobar ICH) diagnosed according to the Boston criteria. We obtained baseline clinical, MRI, and follow-up data on symptomatic lobar ICH. Using Kaplan-Meier and Cox regression analyses, we investigated cSS and ICH risk, adjusting for known confounders.During a median follow-up time of 24 months (interquartile range 9-44 months), 23 of 118 patients (19.5%, 95% confidence interval [CI]: 12.8%-27.8%) experienced symptomatic lobar ICH. Any cSS and disseminated cSS were predictors of time until first or recurrent ICH (log-rank test: p = 0.0045 and p = 0.0009, respectively). ICH risk at 4 years was 25% (95% CI: 7.6%-28.3%) for patients without siderosis; 28.9% (95% CI: 7.7%-76.7%) for patients with focal siderosis; and 74% (95% CI: 44.1%-95.7%) for patients with disseminated cSS (log-rank test: p = 0.0031). In Cox regression models, any cSS and disseminated cSS were both independently associated with increased lobar ICH risk, after adjusting for ≥ 2 microbleeds and age (hazard ratio: 2.53; 95% CI: 1.05-6.15; p = 0.040 and hazard ratio: 3.16; 95% CI: 1.35-7.43; p = 0.008, respectively). These results remained consistent in sensitivity analyses including only patients with symptomatic lobar ICH at baseline.Our findings indicate that cSS, particularly if disseminated, is associated with an increased risk of symptomatic lobar ICH in CAA. cSS may help stratify future bleeding risk in CAA, with implications for prognosis and treatment.
Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss.
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