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1.
ObjectiveTo compare the effect of exercises and orthotics with orthotics alone on pain and hand function in patients with first carpometacarpal joint (CMC-1) osteoarthritis (OA) and to predict outcomes on pain and hand function of exercises and orthotics.DesignProspective cohort study with propensity score matching.SettingData collection took place in 13 outpatient clinics for hand surgery and hand therapy in The Netherlands.ParticipantsA consecutive, population-based sample of patients with CMC-1 OA (N=173) was included in this study, of which 84 were matched on baseline demographics and baseline primary outcomes.InterventionsExercises and orthotics versus orthotics alone.Main Outcome MeasuresPrimary outcomes included pain and hand function at 3 months, measured using visual analog scale (VAS, 0-100) and the Michigan Hand Outcomes Questionnaire (MHQ, 0-100).ResultsA larger decrease in VAS pain at rest (11.1 points difference; 95% confidence interval, 1.9-20.3; P=.002) and during physical load (22.7 points difference; 95% confidence interval, 13.6-31.0; P<.001) was found in the exercise + orthotic group compared to the orthotic group. In addition, larger improvement was found for the MHQ subscales pain, work performance, aesthetics, and satisfaction in the exercise + orthotic group. No differences were found on other outcomes. Baseline scores of metacarpophalangeal flexion, presence of scaphotrapeziotrapezoid OA, VAS pain at rest, heavy physical labor, and MHQ total predicted primary outcomes for the total exercise + orthotic group (N=131).ConclusionsNon-surgical treatment of patients with CMC-1 OA should include exercises, since there is a relatively large treatment effect compared to using an orthosis alone. Future research should study exercises and predictors in a more standardized setting to confirm this finding.  相似文献   
2.
BackgroundImmunizations have led to a decrease in the incidence of invasive meningococcal disease (IMD) in Canada, but this infection still leads to significant morbidity and mortality.ObjectivesThe purpose of this study was to determine the burden of illness and management of IMD in paediatric hospitals.MethodsData were collected on all cases of IMD in eight paediatric hospitals from 2013 to 2017.ResultsThere were 17 cases of IMD. Three of eight hospitals had no cases. Just over half of the cases were serogroup B (n=9); a quarter (n=4) were serogroup W; less than a quarter (n=3) were serogroup Y; and one was unknown. Two infected children were not started on antibiotics until day one and day five after the initial blood culture was collected, but had uneventful recoveries. Six cases required admission to intensive care units; two died. Six cases had probable or proven meningitis. Thrombocytopenia was documented in seven cases. All cases had elevated C-reactive protein levels. Seven children received more than seven days of antibiotics; of these seven, only two had complications that justified prolonged therapy (subdural empyema and septic knee). Six cases had a central line placed.ConclusionIMD is now rare in Canadian children, but about one-third of the cases in our study required treatment in the intensive care unit and two died. Clinicians appear to not always be aware that a five to seven-day course is adequate for uncomplicated cases of bacteremia or meningitis.  相似文献   
3.
《亚太生殖杂志》2014,3(3):176-179
ObjectiveTo study the effect of inter medin(IMD) on smooth muscle of rat seminal vesicles including the specific receptors and the signal pathways involved.MethodsThe contraction of the seminal vesicle in response to norepinephrine (NE) and ADM2/IMD was studied by the organ bath method. The effects of antagonists for calcitonin gene related peptide (CGRP), adrenomedullin (ADM) and IMD receptors, and inhibitors of nitric oxide synthase, [L-NG-Nitroarginine Methyl Ester, L-NAME) and cAMP-dependent protein kinase (PKA), KT5720] were also investigated. The first overshoot, amplitude, frequency and basal tone were measured.ResultsThere is no significant effect of IMD on the initial overshoot, frequency and the basal tone in the seminal vesicle contraction. Only the amplitude of the contraction induced by NE was inhibited by IMD. The IMD inhibitory actions on amplitude were completely blocked by hADM22-52 and L-NAME, but not by hCGRP8-37 or KT5720. Furthermore, the action was diminished by IMD17-47.ConclusionThe results demonstrated that the inhibitory action of IMD on NE-induced seminal vesicle contraction was mediated via the ADM receptor(s) and the nitric oxide production pathway, partially by the IMD receptor, but not by the CGRP receptor and the cAMP-PKA pathway.  相似文献   
4.
目的探讨脂多糖致急性肺损伤大鼠肺泡灌洗液(BALF)中表面蛋A(pulmonary surfactant associated protein A,SP-A)浓度及肺组织单核巨噬细胞中白介素18(interleukin 18,IL-18)的表达水平及中介素1-53(intermedin 1-53.IMD1-53)的影响。方法 将36只雄性Vistar大鼠随机分为正常组(A组)、急性肺损伤组(B组)、中介素1-53干预组(C组),于2h,4h分别测定血气分析,后处死大鼠,测定肺组织湿/干比(W/D)、ELISA法检测BALF中SP-A的浓度、免疫组化法检测肺单核巨噬细胞内IL-18表达及各时间点肺组织病理变化。结果 与A组比较,B组动脉血PO2和BALF中SP-A浓度降低显著(P〈0.05),湿干比及单核巨噬细胞中IL-18表达增加(P〈0.05),肺组织充血水肿明显。与C组相比,上述改变得以逆转,肺损伤程度明显减轻(P〈0.05)。结论中介素1-53可通过抑制SP-A的减少和IL-18的生成在急性肺损伤早期起到一定的保护作用。  相似文献   
5.
目的 探讨急性胰腺炎(AP)患者血清垂体中叶素(IMD)及降钙素原(PCT)动态变化监测的临床价值.方法 选取我院2013年1月至2016年9月急性胰腺炎患者91例作为研究对象,所有患者均于入院时、第3天、第5天、第7天采集静脉血,采用酶联免疫吸附法测定PCT,同时进行APACHEⅡ评分;根据患者急性胰腺炎严重程度分为轻症胰腺炎(MAP)组49例和重症胰腺炎(SAP)组42例.比较两组IMD及PCT动态变化.结果 组内比较,两组患者第3天、第5天、第7天IMD均低于入院时,第3天PCT明显高于入院时,差异均有统计学意义(P<0.05);MAP组第5天、第7天PCT明显低于入院时,SAP组第5天PCT高于入院时,第7天低于入院时,差异均有统计学意义(P<0.05);组间比较,MAP组患者入院时、第3天、第5天、第7天IMD均高于SAP组,PCT均低于SAP组,差异均有统计学意义(P<0.05);MAP组患者24 h APACHEⅡ评分为(4.54±0.98)分,明显低于SAP组的(15.09±3.72)分,差异有统计学意义(P<0.05);MAP组、SAP组APACHEⅡ评分与IMD的相关系数分别为-0.089、-0.118,呈负相关;与PCT相关系数分别为0.194、0.233,呈正相关(P<0.01).结论 血清IMD及PCT可在一定程度上反映AP严重程度及疗效,具有较高的临床价值.  相似文献   
6.
IFN‐γ signaling is essential for the innate immune defense against mycobacterial infections. IFN‐γ signals through the IFN‐γ receptor, which consists of a tetramer of two IFN‐γR1 chains in complex with two IFN‐γR2 chains, where IFN‐γR1 is the ligand‐binding chain of the interferon‐γ receptor and IFN‐γR2 is the signal‐transducing chain of the IFN‐γ receptor. Germline mutations in the gene IFNGR1 encoding the IFN‐γR1 cause a primary immunodeficiency that mainly leads to mycobacterial infections. Here, we review the molecular basis of this immunodeficiency in the 130 individuals described to date, and report mutations in five new individuals, bringing the total number to 135 individuals from 98 kindreds. Forty unique IFNGR1 mutations have been reported and they exert either an autosomal dominant or an autosomal recessive effect. Mutations resulting in premature stopcodons represent the majority of IFNGR1 mutations (60%; 24 out of 40), followed by amino acid substitutions (28%, 11 out of 40). All known mutations, as well as 287 other variations, have been deposited in the online IFNGR1 variation database ( www.LOVD.nl/IFNGR1 ). In this article, we review the function of IFN‐γR1 and molecular genetics of human IFNGR1.  相似文献   
7.
8.

Objective

Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective.

Methods

A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n = 150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%.

Results

A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust.

Conclusions

An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions.  相似文献   
9.

Background

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants.

Methods

Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1–7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%).

Results

A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI −0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference −0.1% [95% CI −4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups.

Conclusion

In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.  相似文献   
10.
We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.  相似文献   
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