Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management.

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials.

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.

Inter-rater reliability of the radiographic assessment of simple bone cysts.

PURPOSE: To develop and evaluate the reliability of an explicit set of parameters and criteria for simple bone cysts (SBCs) and evaluate the reliability of single versus serial chronological reading methods. METHODS: Radiographic criteria were developed based on the literature and expert consensus. A single anteroposterior/lateral radiograph from 32 subjects with SBC were evaluated by three radiologists. A second reading was then conducted using revised criteria including a visual schematic. In the third reading the same images were assessed but radiologists had access to images from two additional time points. Inter-rater reliability was assessed after each reading using kappa (κ) and percentage agreement for categorical and binary parameters and intra-class correlation coefficient (ICC) for continuous parameters. RESULTS: Parameters that were revised with more explicit definitions including the visual schematic demonstrated consistent or improved inter-rater reliability with the exception of continuous cortical rim present and cyst location in the metaphysis and mid-diaphysis. Cortical rim displayed only slight reliability throughout (κ= -0.008 to 0.16). All other categorical parameters had a percentage agreement above 0.8 or a moderate (κ= 0.41 to 0.60), substantial (κ = 0.61 to 0.80) or almost perfect inter-rater reliability (κ = 0.81 to 1.0) in at least one reading. All continuous parameters demonstrated excellent inter-rater reliability (ICC > 0.75) in at least one reading with the exception of scalloping (ICC = 0.37 to 0.70). Inter-rater reliability values did not indicate an obviously superior method of assessment between single and serial chronological readings. CONCLUSION: Explicit criteria for SBC parameters used in their assessment demonstrated improved and substantial inter-rater reliability. Inter-rater reliability did not differ between single and serial chronological readings. LEVEL OF EVIDENCE: Not Applicable.

Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

The long-term outcome of patients treated operatively and non-operatively for scoliosis deformity secondary to spina bifida.

The purpose of this study was to evaluate the long-term outcome of adults with spina bifida cystica (SBC) who had been treated either operatively or non-operatively for scoliosis during childhood. We reviewed 45 patients with a SBC scoliosis (Cobb angle ≥ 50º) who had been treated at one of two children's hospitals between 1991 and 2007. Of these, 34 (75.6%) had been treated operatively and 11 (24.4%) non-operatively. After a mean follow-up of 14.1 years (standard deviation (sd) 4.3) clinical, radiological and health-related quality of life (HRQOL) outcomes were evaluated using the Spina Bifida Spine Questionnaire (SBSQ) and the 36-Item Short Form Health Survey (SF-36). Although patients in the two groups were demographically similar, those who had undergone surgery had a larger mean Cobb angle (88.0º (sd 20.5; 50.0 to 122.0) ; : versus 65.7º (sd 22.0; 51.0 to 115.0); p < 0.01) and a larger mean clavicle-rib intersection difference (12.3 mm; (sd 8.5; 1 to 37); versus 4.1 mm, (sd 5.9; 0 to 16); p = 0.01) than those treated non-operatively. Both groups were statistically similar at follow-up with respect to walking capacity, neurological motor level, sitting balance and health-related quality of life (HRQOL) outcomes. Spinal fusion in SBC scoliosis corrects coronal deformity and stops progression of the curve but has no clear effect on HRQOL.

Testosterone regulates bone response to inflammation.

This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1ß expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function.

Adult hearing screening: follow-up and outcomes1.

PURPOSE: To screen hearing and evaluate outcomes in community-dwelling older adults. METHOD: Three thousand and twenty-five adults responded to an invitation to be screened by questionnaire, otoscopy, and pure-tone audiometry. Pure-tone average (PTA) >35 dB HL in the worse ear, unilateral hearing loss, or otoscopic findings were the criteria for referral for services. A questionnaire related to compliance with referral recommendations was completed by telephone interview for 160 randomly selected participants after 1-2 years from referral. RESULTS: The referral rate for audiologic/hearing aid evaluation was 46%, and referral for cerumen removal/medical evaluation was 17%. Of the people referred for audiologic/hearing aid evaluation, 18% tried a hearing aid; 2 years later, 11% were using a hearing aid. Screening recommendations affected participants' decision to seek help. Study participants stated that the screening was helpful, it should be offered to everybody, and they would participate in future screenings. CONCLUSION: Although adult hearing screening offered timely identification of hearing loss for adults seeking help, follow-up with hearing aid treatment was low.

SURgical interventions with FEIBA (SURF): international registry of surgery in haemophilia patients with inhibitory antibodies.

Factor VIII Inhibitor Bypassing Activity (FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open-label, noninterventional, postauthorization study [SURgical interventions with FEIBA (SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty-five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be 'good' or 'excellent' in 91.2% (31 of 34) of surgical procedures and 'fair' in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events (SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors.

Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study.

BACKGROUND: To examine changes to whole body and regional lean mass (LM) and fat mass (FM) over 33 months of intermittent androgen suppression therapy (IAST). METHODS: Phase II cohort study of 72 prostate cancer patients without metastatic bone disease. Patients received flutamide 250 mg tid and leuprolide 22.5 mg three monthly depot for the 9-month initial treatment phase (iTREAT), at which point patients ceased therapy providing PSA <4 ng ml(-1) with continued monitoring for further 2 years (POST). AST was recommenced when PSA exceeded pretreatment level or ≥ 20 ng ml(-1). Body composition was assessed using dual energy X-ray absorptiometry at baseline, completion of treatment phase, and 1 and 2 years post treatment phase (months 21 and 33). RESULTS: LM decreased by 1.3 kg and FM increased by 2.3 kg (P<0.001) following iTREAT. During the POST period, there were no further adverse effects on LM or FM, but also no recovery to pretreatment levels. Patients who failed to recover testosterone by month 33 experienced a significant increase in FM compared with those who recovered eugonadal levels of testosterone (10 nmol ml(-1); P = 0.019). Change in testosterone was moderately correlated to changes in % FM (r = -0.314, P<0.028) and LM (r = 0.300, P<0.036) during POST phase. Waist circumference progressively increased over time and by 2 years, POST had not recovered to baseline levels. CONCLUSIONS: Loss of LM and gain in FM during the 9-month iTREAT was not reversed during 2-year POST, although further deterioration was not observed. Subgroup analysis identified those recovering testosterone showed some body composition improvements. These findings suggest potential benefits of IAST, where testosterone levels are able to recover, to reduce the ongoing adverse effects on body composition, such as the acceleration of sarcopenia and risks associated with metabolic disease.

Tinnitus complaint behaviour in long-standing Menière's disorder: its association with the other cardinal symptoms.

OBJECTIVE: To explore factors that determines tinnitus complaint behaviour in patients with chronic long-standing Menière's disorder. DESIGN AND SETTING: A questionnaire-based cross-sectional investigation. This included the Oto-neurological questionnaire, the Hearing Disability and Handicap Scale (HDHS), Hearing Measurement Scale (HMS) on sound localisation and the Dizziness Handicap Questionnaire (DHQ). PARTICIPANTS: Randomly selected 183 members of the Finnish Menière's Federation. INTERVENTION: Postal questionnaire. MAIN OUTCOME MEASURE: International Tinnitus Inventory and impact of tinnitus. RESULTS: The 183 patients,[36 men and 147 women; mean age, 63 years] had their Meniere's disorder-like symptoms, with a mean of 18 years [range, 1-43], 19% of patients ranked tinnitus as their most severe symptom, and 10% experienced tinnitus as causing a severe or very severe impact. Regression analysis indicated that 41% of International Tinnitus Inventory variance and 28% of tinnitus impact variance were explained by the cardinal symptoms of Menière's disorder. Furthermore, 40% of International Tinnitus Inventory and 25% of tinnitus impact variance were explained by symptom-related disabilities (HDHS, HMS and DHQ). Aural pressure, hearing loss and gait problems were the most important predictors of tinnitus complaint. Understanding what people say and limitation of activities because of vertigo were the most important related disabilities. CONCLUSION: Tinnitus shares a significant variance with the other cardinal symptoms in patients with long-standing Menière's disorder. As the impact is significantly related to activity limitations based on hearing disability and vertigo, the results suggest that therapeutic efforts to reduce tinnitus in Menière's disorder should include the alleviation of balance and hearing problems.

The patient journey of adults with hearing impairment: the patients' views.

OBJECTIVE: The term 'patient journey' refers to the experiences and processes the patient goes through during the course of a disease and its treatment. The study explores the perspectives of adults with acquired hearing impairment and to further develop the patient journey template based on the Ida model. DESIGN: Qualitative approach using thematic analysis and process mapping. SETTING: Support groups of people with hearing impairment. PARTICIPANTS: Thirty-two adults with acquired hearing impairment from two hearing impaired groups in Wales. All were hearing aid users. MAIN OUTCOME MEASURE: Participants worked in small groups to describe their experiences through hearing loss. These data were used to develop a template of the patients' perspective of the journey. This was then compared with the perspective of professionals, and a 'patient journey template for adults with acquired hearing impairment' was developed. RESULTS: This template identifies seven main phases as follows: (i) pre-awareness; (ii) awareness; (iii) movement; (iv) diagnostics; (v) rehabilitation; (vi) self-evaluation; and (vii) resolution. The study identified a number of new components. The self-evaluation component was not defined by professionals and reflects the need for patients to consider the costs, benefits and alternatives to the approach provided by audiologists. It is important for audiologists to be aware of this. CONCLUSION: The study highlighted the differences and commonalities in perspectives of professionals and patients. Use of the patient journey can help clinicians to understand the unique experiences their patients go through help them to develop patient-centred treatment.

Robot-assisted laparoscopic ureterolysis: case report and literature review of the minimally invasive surgical approach.

OBJECTIVES: To evaluate our case of robot-assisted ureterolysis (RU), describe our surgical technique, and review the literature on minimally invasive ureterolysis. METHODS: One patient managed with robot-assisted ureterolysis for idiopathic retroperitoneal fibrosis was identified. The chart was analyzed for demographics, operative parameters, and immediate postoperative outcome. The surgical technique was assessed and modified. Lastly, a review of the published literature on ureterolysis managed with minimally invasive surgery was performed. RESULTS: One patient underwent robot-assisted ureterolysis at our institution in 2 separate settings. Operative time (OR) decreased from 279 minutes to 191 minutes. Estimated blood loss (EBL) was less than 50 mL. The patient has been free of symptoms and both renal units are unobstructed. According to the published literature, 302 renal units underwent successful laparoscopic ureterolysis (LU), and 6 renal units underwent RU. There were 9 open conversions (all in LU). Mean OR in LU was 248 minutes for unilateral and 386 minutes for bilateral cases. In RU, mean OR was 220 minutes for unilateral and 390 minutes for bilateral cases. EBL averaged 200 mL in LU and 30 mL in RU. CONCLUSIONS: Our data reveal that robot-assisted ureterolysis is safe and feasible. Published data demonstrate the advantages of minimally invasive surgery.

Exploring beyond viral load testing for EBV lymphoproliferation: role of serum IL-6 and IgE assays as adjunctive tests.

We examined serum IL-6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL-6, and IgE assays were compared between PTLD cases and non-cases at <3, 3-6 and >6 months after transplantation. Median IL-6 levels in PTLD cases were 15.5 (2.0-87.1) and 23.3 (2.1-276) pg/mL compared with 3.25 (0.92-114) and 3.5 (0.75-199.25) pg/mL in non-cases at 3-6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL-6 levels correlated with VL and PTLD occurrence (Spearman's coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL-6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL-6 levels can improve the clinician's ability to identify PTLD, among patients with elevated EBV viral loads.

Use of a closed set questionnaire to measure primary and secondary effects of neurofibromatosis type 2.

OBJECTIVES: To identify the greatest difficulties reported by people affected by neurofibromatosis type 2, and to determine the relationship between the primary and secondary effects of the disease. DESIGN: Postal questionnaire study. SETTING: Questionnaire sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult patients under the care of the Manchester multidisciplinary neurofibromatosis type 2 team were invited to take part. MAIN OUTCOME MEASURE: The response rate was 62 out of 87 (71 per cent). RESULTS: Respondents' answers emphasised that their greatest problem was deafness, which resulted in communication difficulties with social contacts, close partners, family and friends. Correlation coefficients indicated a relationship between general mood changes and hearing difficulties, social communication problems, balance difficulties and mobility problems. Self-confidence was significantly related only to social communication problems. CONCLUSIONS: The use of a closed set neurofibromatosis type 2 questionnaire identified hearing problems and subsequent communication difficulties as the main problems faced by people with this condition.

Alpha1- and alpha2-containing GABAA receptor modulation is not necessary for benzodiazepine-induced hyperphagia.

Benzodiazepines increase food intake, an effect attributed to their ability to enhance palatability. We investigated which GABA(A) receptor subtypes may be involved in mediating benzodiazepine-induced hyperphagia. The role of the alpha2 subtype was investigated by observing the effects of midazolam, on the behavioural satiety sequence in mice with targeted deletion of the alpha2 gene (alpha2 knockout). Midazolam (0.125, 0.25 and 0.5mg/kg) increased food intake and the amount of time spent feeding in alpha2 knockout mice, suggesting that BZ-induced hyperphagia does not involve alpha2-containing GABA(A) receptors. We further investigated the roles of alpha1- and alpha3-containing GABA(A) receptors in mediating BZ-induced hyperphagia. We treated alpha2(H101R) mice, in which alpha2-containing receptors are rendered benzodiazepine insensitive, with L-838417, a compound which acts as a partial agonist at alpha2-, alpha3- and alpha5-receptors but is inactive at alpha1-containing receptors. L-838417 (10 and 30 mg/kg) increased food intake and the time spent feeding in both wildtype and alpha2(H101R) mice, demonstrating that benzodiazepine-induced hyperphagia does not require alpha1- and alpha2-containing GABA(A) receptors. These observations, together with evidence against the involvement of alpha5-containing GABA(A) receptors, suggest that alpha3-containing receptors mediate BZ-induced hyperphagia in the mouse.

Comparative analysis of surgical margins between radical retropubic prostatectomy and RALP: are patients sacrificed during initiation of robotics program?

OBJECTIVES: To compare the incidence of positive surgical margins obtained with robotic-assisted laparoscopic prostatectomy (RALP), during the initiation of a robotics program, with that from a similarly matched cohort of open radical retropubic prostatectomy (RRP) cases as performed by a single surgeon. METHODS: From December 2005 to March 2008, 63 patients underwent RRP and another 50 underwent RALP by a single urologist. The records were retrospectively reviewed, and 50 RRP patients were selected from the RRP group whose records were similar to the records of the 50 patients who had undergone RALP. We compared the incidence of positive surgical margins and the location of positive margins among the 2 groups. Additional variables evaluated included the preoperative prostate-specific antigen level, preoperative Gleason score, clinical stage, postoperative Gleason score, tumor volume, and pathologic stage. RESULTS: The positive margin rate for the RRP group was 36% compared with 22% for the RALP group (P = .007). The incidence of positive margins for pathologic Stage pT2c disease in the RALP group was 22.8% compared with 42.8% in the RRP group, a statistically significant difference (P = .006). Fewer positive margins were found in the RALP Gleason score 7 group than in the RRP group, 29% vs 60%, again a statistically significant difference (P = .003). CONCLUSIONS: We present our series comparing a single urologist's positive margin rates during the learning curve of a robotics program with his experience of a similarly matched cohort of RRP patients. A statistically significant lower positive margin rate can be achieved in RALP patients even during the learning period.

MRI in the diagnosis of pediatric multiple sclerosis.

BACKGROUND: MRI diagnostic criteria have not yet been adopted for pediatric multiple sclerosis (MS). MRI plays a pivotal role in supporting the diagnosis of MS in adults. We sought to quantitatively define the MRI features of pediatric MS, to determine features that distinguish MS from nondemyelinating relapsing childhood neurologic disorders, and to propose MRI criteria for lesion dissemination in space in children with MS. METHODS: A retrospective analysis of MRI scans from 38 children with clinically definite MS and 45 children with nondemyelinating diseases with relapsing neurologic deficits (migraine, systemic lupus erythematosus) was performed. For each scan, T2/FLAIR hyperintense lesions were quantified and categorized according to location and size. Mean lesion counts in specific locations were compared between groups to derive diagnostic criteria. Validation of the proposed criteria was performed using MRI scans from a second independent MS cohort (n = 21). RESULTS: MRI lesion location and size categories differed between children with MS and nondemyelinating controls with a medium to large effect size for most variables. The presence of at least two of the following-five or more lesions, two or more periventricular lesions, or one brainstem lesion-distinguished MS from other nondemyelinating disease controls with 85% sensitivity and 98% specificity. CONCLUSIONS: We propose modifications to the currently established McDonald MRI criteria for lesion dissemination in space that will enhance the diagnostic accuracy of these criteria for multiple sclerosis in children.

The relationship between changes in self-rated quality of life after cochlear implantation and changes in individual complaints.

OBJECTIVES: To evaluate the changes in self-rated quality of life (QoL) obtained following cochlear implantation in relation to changes in the individual's complaints. DESIGN: We have used repeated responses over a period of at least 4 years following implantation so as to examine within-subject relationships. PARTICIPANTS: Twenty-four consecutive post-lingually deafened patients who had been fitted with cochlear implants between 1991 and December 2000 at the University Hospital of Wales were investigated. MAIN OUTCOME MEASURES: The open-ended problems questionnaire was used to assess what hearing impaired people themselves considered to be the main problems arising from their hearing loss. The participants were asked to rate the severity of each one of these problems as well as QoL on '0' to '100' visual analogue scales. Both the individual problem ratings and the ratings of QoL were re-administered to the subjects at each follow-up session. RESULTS: Changes in the rated QoL of all patients were significantly associated with changes in specific complaints, for example, the ability to communicate, feeling of isolation, telephone use, self-confidence, enjoyment of music and watching the TV. Multiple stepwise regression analysis showed that, after implantation, improvements in communication abilities, reduced psychological problems and improvements in abilities of daily life were the key determinants of QoL improvement for individual cochlear implant patients. These key predictors reached a plateau at about 1.5-3 years after cochlear implantation. CONCLUSIONS: The relationships between changes in specific complaints and the QoL in individual implantees were highlighted. We suggest that cochlear implant outcome measures should continue for at least 3 years after implantation.