Effectiveness of manual therapies: the UK evidence report

<p>Abstract</p> <p>Background</p> <p>The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions.</p> <p>Methods</p> <p>The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs.</p> <p>Results</p> <p>By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines.</p> <p>Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments.</p> <p>Conclusions</p> <p>Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation, or for Stage 1 hypertension when added to an antihypertensive diet. In children, the evidence is inconclusive regarding the effectiveness for otitis media and enuresis, and it is not effective for infantile colic and asthma when compared to sham manipulation.</p> <p>Massage is effective in adults for chronic low back pain and chronic neck pain. The evidence is inconclusive for knee osteoarthritis, fibromyalgia, myofascial pain syndrome, migraine headache, and premenstrual syndrome. In children, the evidence is inconclusive for asthma and infantile colic.</p

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

White noise speech illusions: A trait-dependent risk marker for psychotic disorder?

Introduction: White noise speech illusions index liability for psychotic disorder in case-control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02-1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79-1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85-1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09-1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84-1.05; ORlow cognitive ability 1.43, 95% CI 1.23-1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82-1.04; ORhigh adversity 1.31, 95% CI 1.13-1.52). A similar, although less marked, pattern was seen for categorical patient-control and sibling-control comparisons. Exposure to recent life events did not modify the association between white noise and familial risk (p interaction = 0.232). Conclusion: The association between white noise speech illusions and familial risk is contingent on additional evidence of endophenotypic expression and of exposure to childhood adversity. Therefore, speech illusions may represent a trait-dependent risk marker

Reccurrence Pattern After Adjuvant Customized Chemotherapy Based on BRCA Expression Level (SCAT Trial)

Background Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement, (St II-IIIA). Customization is feasible in adjuvant setting (tissue availability) . Analysis of expressionin genes involved in DNA repair could be use to select CT regiment. •BRCA1 plays an important role in DNA repair pathways and functions as a differential regulator of response to cisplatin and antimicrotubuleagents. SCAT trial results found that for low BRCA1 levels subgroup Cis-Gemcitabine was superior to Cis-Docetaxel and in high BRCA1 levels subgroup Docetaxel single agent without platinum achieved similar survival to Cis-Doc. Analysis of recurrence pattern in different subgroups of the trials has been performed. Method From Jun/2007 to May/2013 591 patients were screened and 500 p were included (108 in Control arm treated with Cisplatin-Docetaxel and 392 in Experimental arm treated with Cisplatin-Gemcitabine, Cisplatin-Docetaxel or Docetaxel alone according terciles BRCA1 expression level). With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence pattern are analysed in each arm and subgroup treatment and comparison are made for incidence of risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and site of metastases (liver, bone, brain). Result Cumulative recurrence 232/456 evaluable patients (p) (50.8%). Recurrence were seen in 182/354 patients treated in experimental arm and in 50/102 p treated in the control arm (RR 1.04; 0.83-1.30) (p=0.672). Majority of recurrences 159/232 (68.5%) were single site recurrence. Intrathoracic recurrences in 121/232 (52%) while extrathoracic metastatic disease 111/232 (47.8%). No significant differences were seen for single/multiple, intra/extrathoracic recurrences between experimental and control arm. More frequent distant metastatic sites were: bone (42 p), brain (38 p) and liver (11 p) In the experimental group between different treatments no significant differences were found for the overall metastatic rate or for the single/multiple, intrathoracic/extrathoracic recurrences. For specific metastatic sites related to experimental treatment a significant reduction of risk of brain metastases were found in the experimental group with high level BRCA1 treated with Docetaxel single agent (p=0.0016). Conclusion For NSCLC resected patients with lymph node involvement (Stages II-IIIA) risk of recurrence remains high with cumulative rate >50%. There were no differences in the Relative Risk (1.04) of recurrence when control and experimental arm are compared. Majority of recurrences were single site (68.5%) and intrathoracic (52%) but distant metastases developed in 47.8% os p. More frequent metastatic site was bone, followed by brain and liver. Brain metastases risk were significant lower for patients with low BRCA1 expression treated with single agent Docetaxel