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每至年终，各大权威媒体、杂志、学术机构均会纷纷推出其所谓的“十大（Top 10）”，以帮助人们回顾当年度发生的最具里程碑意义的事件、研究和学术进展，本报的国际国内医学十大新闻亦将于2012年1月5日公布。在梳理《自然·医学》（Nat Med）、《柳叶刀》（Lancet）、《科学》（Science）、《时代》（TIMES）、Medscape等或专业或大众的期刊及网站2011年度医学进展Top 10的过程中，编辑惊喜地发现，在这些国外知名媒体所推选出的临床医学研究中，本报各周刊均几乎进行过相关报道，其中，“早期抗病毒治疗可有效预防艾滋病传播”的条目更是登上了包括本报在内多个Top 10之榜。
Curr Opin Allergy Clin Immunol. 2011 Feb;11(1):46-52.
Bronchial provocation testing: the future.
Anderson SD, Brannan JD.
Department of Respiratory & Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
PURPOSE OF REVIEW: Performing a bronchial provocation test (BPT) using a direct or indirect stimulus to identify bronchial hyper-responsiveness (BHR) reduces the possibility of over and under-diagnosis of asthma based on history and symptoms. This review discusses some long-held beliefs of BPTs to include or exclude a diagnosis of asthma or exercise-induced bronchoconstriction (EIB).
RECENT FINDINGS: A high frequency of negative methacholine tests has been reported in 240 patients given a diagnosis of asthma at the end of the study, many of whom had documented EIB. This suggests that a negative methacholine test should not be relied upon to rule out asthma. Further, a positive methacholine test alone should be interpreted with caution as it may reflect airway injury rather than asthma or EIB. Mannitol, an indirect stimulus, identified a similar prevalence of BHR to methacholine and identified more patients than a single exercise test in three studies. However, neither mannitol nor methacholine identified all patients with EIB. Mannitol has a higher specificity for a physician diagnosis of asthma than methacholine.
SUMMARY: It is likely that both a direct test and an indirect test result may be required in some patients in order to confirm or exclude a diagnosis of asthma with certainty.
Arch Intern Med. 2011 Mar 14;171(5):396-403.
Early start of hemodialysis may be harmful.
Rosansky SJ, Eggers P, Jackson K, Glassock R, Clark WF.
Dorn Research Institute, Wm. Jennings Bryan Dorn Veterans Hospital, 526 N Trenholm Rd, Columbia, SC 29206, USA.
BACKGROUND: A dramatic increase in the "early start" of dialysis with an estimated glomerular filtration rate (eGFR) at least 10 mL/min/1.73 m(2) has occurred in the United States since at least 1996. Several recent studies have reported a comorbidity-adjusted survival disadvantage of early start of dialysis. The current study examines a relatively "healthy" dialysis cohort to minimize confounding issues and determine whether early initiation of hemodialysis is associated with a survival benefit or harm.
METHODS: We examined demographics, year of dialysis initiation, primary etiology of renal failure, and body mass index, hemoglobin, and serum albumin levels in 81,176 nondiabetic, 20- to 64-year-old, in-center incident hemodialysis patients with no reported comorbidity besides hypertension. We compared survival, using a piecewise proportional hazards model to estimate covariate-adjusted mortality hazard ratios (HRs) for eGFR at the time of initiation of dialysis. We also performed time-dependent adjusted analysis stratified by initial serum albumin levels lower than 2.5 g/dL, 2.5 to 3.49 g/dL, and 3.5 g/dL or higher (the "healthiest" group [HG]).
RESULTS: Unadjusted 1-year mortality by eGFR ranged from 6.8% in the reference group (eGFR <5.0 mL/min/1.73 m(2)) to 20.1% in the highest eGFR group (≥15.0 mL/min/1.73 m(2)). Compared with the reference group, the HR for the HG was 1.27 (eGFR, 5.0-9.9 mL/min/1.73 m(2)), 1.53 (eGFR, 10.0-14.9 mL/min/1.73 m(2)), and 2.18 (eGFR ≥15.0 mL/min/1.73 m(2)) and ranged from 1.50 to 3.53 mL/min/1.73 m(2) in the first year of dialysis for the early-start group.
CONCLUSION: The increased HR during hemodialysis associated with early start in the healthiest group of patients undergoing dialysis indicates that early start of dialysis may be harmful.
Neurology. 2011 Oct 11;77(15):1473-81.
Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome.
Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators.
St. Joseph’s Hospital Medical Center and Barrow Neurological Institute, Phoenix, AZ, USA.
OBJECTIVE: To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS).
METHODS: Patients aged 2-60 years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases, followed by a 2- or 3-week taper or continuation in an open-label extension. Primary endpoint was percentage decrease in mean weekly drop seizure rates during maintenance vs baseline phases for modified intention-to-treat (mITT) population. Secondary outcomes included other seizure types, responder rates, and physicians' and caregivers' global assessments.
RESULTS: A total of 305 patients were screened, 238 were randomized, and 217 composed the mITT population. Of patients enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p = 0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Responder rates (≥50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6% (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Physicians' and caregivers' assessments indicated clobazam significantly improved symptoms. Somnolence, pyrexia, upper respiratory infections, and lethargy were the most frequent adverse events reported for clobazam.
CONCLUSIONS: Clobazam significantly decreased weekly drop seizure rates in LGS. No new safety signals were identified.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.
Ann Rheum Dis. 2011 Mar;70(3):404-13.
American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials.
Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, Aletaha D, Allaart CF, Bathon J, Bombardieri S, Brooks P, Brown A, Matucci-Cerinic M, Choi H, Combe B, de Wit M, Dougados M, Emery P, Furst D, Gomez-Reino J, Hawker G, Keystone E, Khanna D, Kirwan J, Kvien TK, Landewé R, Listing J, Michaud K, Martin-Mola E, Montie P, Pincus T, Richards P, Siegel JN, Simon LS, Sokka T, Strand V, Tugwell P, Tyndall A, van der Heijde D, Verstappen S, White B, Wolfe F, Zink A, Boers M.
Correspondence to Maarten Boers, Department of Epidemiology and Biostatistics, VU University Medical Center, PK 6Z 165, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
OBJECTIVE: Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition.
METHODS: A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes.
RESULTS: Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3.
CONCLUSION: We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.
Lancet. 2011 Jun 4;377(9781):1938-47.
Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study.
Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR.
Department of Neurological Surgery, Kentucky Spinal Cord Research Center, University of Louisville, KY, USA.
BACKGROUND: Repeated periods of stimulation of the spinal cord and training increased the ability to control movement in animal models of spinal cord injury. We hypothesised that tonic epidural spinal cord stimulation can modulate spinal circuitry in human beings into a physiological state that enables sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks.
METHODS: A 23-year-old man who had paraplegia from a C7-T1 subluxation as a result of a motor vehicle accident in July 2006, presented with complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. After 170 locomotor training sessions over 26 months, a 16-electrode array was surgically placed on the dura (L1-S1 cord segments) in December 2009, to allow for chronic electrical stimulation. Spinal cord stimulation was done during sessions that lasted up to 250 min. We did 29 experiments and tested several stimulation combinations and parameters with the aim of the patient achieving standing and stepping.
FINDINGS: Epidural stimulation enabled the man to achieve full weight-bearing standing with assistance provided only for balance for 4·25 min. The patient achieved this standing during stimulation using parameters identified as specific for standing while providing bilateral load-bearing proprioceptive input. We also noted locomotor-like patterns when stimulation parameters were optimised for stepping. Additionally, 7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation.
INTERPRETATION: Task-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity. These interventions could be a viable clinical approach for functional recovery after severe paralysis.
FUNDING: National Institutes of Health and Christopher and Dana Reeve Foundation.
N Engl J Med. 2011 Nov 17;365(20):1863-75.
First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.
Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Nhamuave A, Quelhas D, Bassat Q, Mandjate S, Macete E, Alonso P, Abdulla S, Salim N, Juma O, Shomari M, Shubis K, Machera F, Hamad AS, Minja R, Mtoro A, Sykes A, Ahmed S, Urassa AM, Ali AM, Mwangoka G, Tanner M, Tinto H, D'Alessandro U, Sorgho H, Valea I, Tahita MC, Kaboré W, Ouédraogo S, Sandrine Y, Guiguemdé RT, Ouédraogo JB, Hamel MJ, Kariuki S, Odero C, Oneko M, Otieno K, Awino N, Omoto J, Williamson J, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Nekoye O, Gondi S, Otieno A, Ogutu B, Wasuna R, Owira V, Jones D, Onyango AA, Njuguna P, Chilengi R, Akoo P, Kerubo C, Gitaka J, Maingi C, Lang T, Olotu A, Tsofa B, Bejon P, Peshu N, Marsh K, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Ayamba S, Kayan K, Owusu-Ofori R, Dosoo D, Asante I, Adjei G, Adjei G, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Kilavo H, Mahende C, Liheluka E, Lemnge M, Theander T, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Agyekum A, Owusu L, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Msika A, Jumbe A, Chome N, Nyakuipa D, Chintedza J, Ballou WR, Bruls M, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Vekemans J, Carter T, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, Vansadia P; RTS,S Clinical Trials Partnership.
Albert Schweitzer Hospital, Lambarene, Gabon.
BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries.
METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories.
RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64).
CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).