A multi-level approach to program objectives: definitions and managerial implications

Projects are recognized as the building blocks of strategy. Outputs, outcomes, benefits and related concepts have been put forward by the program management community to bridge the gap between strategy and projects. Yet, firstly there appears to be some discordance among authors on the exact nature of these concepts. Secondly, these frameworks may not yet fully reflect the specific nature of strategy implementation. Therefore it is hard to accept them as the basis for communication between the project/program organisation and the business management when managing strategy implementation through programs of projects. We will borrow three concepts (resources, competencies and capabilities) from the resource based view of the company (RBV). We shall use them to define three levels of program objectives. We will illustrate these levels through a case of a strategic program in a professional information services company. We conclude with implications on current program management practice and research. Keywords: program management, program objectives, strategy implementation, benefits managemen

The effect of physical therapy treatment in patients with subjective tinnitus:A systematic review

Background: Tinnitus is a very common symptom that often causes distress and decreases the patient's quality of life. Apart from the well-known causes, tinnitus can in some cases be elicited by dysfunctions of the cervical spine or the temporomandibular joint (TMJ). To date however, it is unclear whether alleviation of these dysfunctions, by physical therapy treatment, also decreases the tinnitus complaints. Such physical therapy could be an interesting treatment option for patients that are now often left without treatment. Objectives: The aim of this review was to investigate the current evidence regarding physical therapy treatment in patients with tinnitus. Data sources: The online databases Pubmed, Web of Science, Cochrane, and Embase were searched up to March 2016. Two independent reviewers conducted the data extraction and methodological quality assessment. Study eligibility criteria: Only randomized controlled trials and quasi-experimental trials were included in the review. Studies had to be written in English, French, Dutch, or German. Participants and interventions: The included studies investigated the effect of physical therapy treatment modalities on tinnitus severity in patients suffering from subjective tinnitus. Results: Six studies were included in this review, four investigating cervical spine treatment and two investigating TMJ treatment. These studies show positive effects of cervical spine treatment (manipulations, exercises, triggerpoint treatment) on tinnitus severity. Additionally, decrease in tinnitus severity and intensity was demonstrated after TMJ treatment, following splints, occlusal adjustments as well as jaw exercises. Limitations: The risk of bias in the included studies was high, mainly due to lack of randomization, lack of blinding of subjects, therapists, and/or investigators. Additionally, risk of bias is present due to incomplete presentation of the data and selective reporting. A major issue of the reviewed papers is the heterogeneity of the included study populations, treatments and outcome measures, which inhibit data pooling and meta-analysis. Conclusions: Despite the methodological issues in the included studies and the consequent low quality evidence, it is noteworthy that all included studies show positive treatment effects. Before recommendations can be made, these results need to be confirmed in larger, high quality studies, using unambiguous inclusion criteria, state-of-the-art treatment, and high quality outcome measures

Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Central sensitization has recently been documented in patients with knee osteoarthritis (OAk). So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients.</p> <p>Methods</p> <p>Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens). Follow-up measurements will be scheduled after a period of 6 and 12 weeks.</p> <p>Discussion</p> <p>Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01390285">NCT01390285</a></p

IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia

Aims: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs. Methods and results: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16–1.89; P = 0.313). Conclusions: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs

Design as a provocation to support discussion about euthanasia: The Plug

Design as a provocation to support discussion about euthanasia: The Plu

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis

Background & AimsEtrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did.MethodsWe performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1.ResultsColon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell−associated genes than patients who did not respond (P < .05). Colonic CD4+ integrin αE+ cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4+ αE− cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMAhigh vs 19% GZMAlow and 44% ITGAEhigh vs 19% ITGAElow). Compared with ITGAElow and GZMAlow patients, patients with ITGAEhigh and GZMAhigh had higher baseline numbers of epithelial crypt-associated integrin αE+ cells (P < .01 for both), but a smaller number of crypt-associated integrin αE+ cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%−80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline.ConclusionsLevels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarkerhigh patients. Larger, prospective studies of markers are needed to assess their clinical value

Bioethical implications of end-of-life decision-making in patients with dementia:a tale of two societies

End-of-life decision-making in patients with dementia is a complex topic. Belgium and the Netherlands have been at the forefront of legislative advancement and progressive societal changes concerning the perspectives toward physician-assisted death (PAD). Careful consideration of clinical and social aspects is essential during the end-of-life decision-making process in patients with dementia. Geriatric assent provides the physician, the patient and his family the opportunity to end life with dignity. Unbearable suffering, decisional competence, and awareness of memory deficits are among the clinical considerations that physicians should incorporate during the end-of-life decision-making process. However, as other societies introduce legislature granting the right of PAD, new social determinants should be considered; Mexico City is an example. Current perspectives regarding advance euthanasia directives (AED) and PAD in patients with dementia are evolving. A new perspective that hinges on the role of the family and geriatric assent should help culturally heterogeneous societies in the transition of their public health care policies regarding end-of-life choices.</p

Dwelling, house and home: towards a home-led perspective on dementia care

“Home” is well known from everyday experience, plays a crucial role in all kinds of narratives about human life, but is hardly ever systematically dealt with in the philosophy of medicine and health care. The notion of home is ambiguous, is often used in a metaphorical way, and is closely related to concepts such as house and dwelling. In this paper the phenomenon of home is explored by means of some phenomenological writings of Heidegger, Bollnow, Bachelard and Levinas. Common in their views is that being at home and dwelling mean something more fundamental than an activity we do along with other activities, such as working and travelling. Dwelling, building a house and being at home are fundamental aspects of human existence. Being human is dwelling. While exploring the relevance of this phenomenological perspective for medical theory and practice, the focus is on the care of people suffering from dementia