A complex regional intervention to implement advance care planning in one town's nursing homes: Protocol of a controlled inter-regional study

<p>Abstract</p> <p>Background</p> <p>Advance Care Planning (ACP) is an emerging strategy to ensure that well-reflected, meaningful and clearly documented treatment preferences are available and respected when critical decisions about life-sustaining treatment need to be made for patients unable to consent. In Germany, recent legislation confirms that advance directives (AD) have to be followed if they apply to the medical situation, but implementation of ACP has not yet been described.</p> <p>Methods/Design</p> <p>In a longitudinal controlled study, we compare 1 intervention region (4 nursing homes [n/hs], altogether 421 residents) with 2 control regions (10 n/hs, altogether 985 residents). Inclusion went from 01.02.09 to 30.06.09, observation lasted until 30.06.10. Primary endpoint is the prevalence of ADs at follow-up, 17 (12) months after the first (last) possible inclusion. Secondary endpoints compare relevance and validity of ADs, process quality, the rate of life-sustaining interventions and, in deceased residents, location of death and intensity of treatment before death. The regional multifaceted intervention on the basis of the US program Respecting Choices^®comprises training of n/h staff as facilitators, training of General Practitioners, education of hospital and ambulance staff, and development of eligible tools, including Physician Orders for Life-Sustaining Treatment in case of Emergency (POLST-E).</p> <p><it>Participation data: </it>Of 1406 residents reported to live in the 14 n/hs plus an estimated turnover of 176 residents until the last possible inclusion date, 645 (41%) were willing to participate. Response rates were 38% in the intervention region and 42% in the control region. Non-responder analysis shows an equal distribution of sex and age but a bias towards dependency on nursing care in the responder group. <it>Outcome analysis </it>of this study will become available in the course of 2011.</p> <p>Discussion</p> <p>Implementing an ACP program for the n/hs and related health care providers of a region requires a complex community intervention with the effect of nothing less than a cultural shift in this health care sector. This study is to our knowledge the first to develop a strategy for regional implementation of ACP, and to evaluate its feasibility in a controlled design.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN99887420">ISRCTN99887420</a></p

Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases

Infliximab is a monoclonal antibody directed against TNF-α. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role

Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? - Results of a randomized controlled pilot trial

Background: Uncomplicated lower urinary tract infections (UTI) are usually treated with antibiotics. However, there is little evidence for alternative therapeutic options. This pilot study was set out 1) to make a rough estimate of the equivalence of ibuprofen and ciprofloxacin for uncomplicated urinary tract infection with regard to symptom resolution, and 2) to demonstrate the feasibility of a double-blind, randomized controlled drug trial in German general practices. Methods: We performed a double-blind, randomized controlled pilot trial in 29 German general practices. Eighty otherwise healthy women aged 18 to 85 years, presenting with at least one of the main UTI symptoms dysuria and frequency and without any complicating factors, were randomly assigned to receive either ibuprofen 3 x 400 mg oral or ciprofloxacin 2 x 250 mg (+1 placebo) oral, both for three days. Intensity of main symptoms-dysuria, frequency, low abdominal pain-was recorded at inclusion and after 4, 7 and 28 days, scoring each symptom from 0 (none) to 4 (very strong). The primary endpoint was symptom resolution on Day 4. Secondary outcomes were the burden of symptoms on Days 4 and 7 (based on the sum score of all symptoms), symptom resolution on Day 7 and frequency of relapses. Equivalence margins for symptom burden on Day 4 were pre-specified as +/-0.5 sum score points. Data analysis was done by intention to treat and per protocol. Randomization was carried out on patient level by computer programme in blocks of six. Results: Seventy-nine patients were analyzed (ibuprofen n = 40, ciprofloxacin n = 39). On Day 4, 21/36 (58.3%) of patients in the ibuprofen-group were symptom-free versus 17/33 (51.5%) in the ciprofloxacin-group. On Day 4, ibuprofen patients reported fewer symptoms in terms of total sum score (1; SD 1,42) than ciprofloxacin patients (1,3; SD 1,9), difference-0,33 (95% CI (-1,13 to + 0,47)), PP (per protocol) analysis. During Days 0 and 9, 12/36 (33%) of patients in the ibuprofen-group received secondary antibiotic treatment due to ongoing or worsening symptoms, compared to 6/33 (18%) in the ciprofloxacin-group (non significant). A total of 58 non-serious adverse events were reported, 32 in the ibuprofen group versus 26 in the ciprofloxacin group (non significant). Conclusions: Our results support the assumption of non-inferiority of ibuprofen compared to ciprofloxacin for treatment of symptomatic uncomplicated UTI, but need confirmation by further trials

Computing Power and Sample Size for Case-Control Association Studies with Copy Number Polymorphism: Application of Mixture-Based Likelihood Ratio Test

Recent studies suggest that copy number polymorphisms (CNPs) may play an important role in disease susceptibility and onset. Currently, the detection of CNPs mainly depends on microarray technology. For case-control studies, conventionally, subjects are assigned to a specific CNP category based on the continuous quantitative measure produced by microarray experiments, and cases and controls are then compared using a chi-square test of independence. The purpose of this work is to specify the likelihood ratio test statistic (LRTS) for case-control sampling design based on the underlying continuous quantitative measurement, and to assess its power and relative efficiency (as compared to the chi-square test of independence on CNP counts). The sample size and power formulas of both methods are given. For the latter, the CNPs are classified using the Bayesian classification rule. The LRTS is more powerful than this chi-square test for the alternatives considered, especially alternatives in which the at-risk CNP categories have low frequencies. An example of the application of the LRTS is given for a comparison of CNP distributions in individuals of Caucasian or Taiwanese ethnicity, where the LRTS appears to be more powerful than the chi-square test, possibly due to misclassification of the most common CNP category into a less common category

C2 and CFB Genes in Age-Related Maculopathy and Joint Action with CFH and LOC387715 Genes

BackgroundAge-related maculopathy (ARM) is a common cause of visual impairment in the elderly populations of industrialized countries and significantly affects the quality of life of those suffering from the disease. Variants within two genes, the complement factor H (CFH) and the poorly characterized LOC387715 (ARMS2), are widely recognized as ARM risk factors. CFH is important in regulation of the alternative complement pathway suggesting this pathway is involved in ARM pathogenesis. Two other complement pathway genes, the closely linked complement component receptor (C2) and complement factor B (CFB), were recently shown to harbor variants associated with ARM.Methods/principal findingsWe investigated two SNPs in C2 and two in CFB in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in C2, to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis suggested that accounting for the effect at this locus significantly (P-value 0.002) improves the fit of a genetic risk model of CFH and LOC387715 effects only. Modeling with the generalized multifactor dimensionality reduction method showed that adding C2 to the two-factor model of CFH and LOC387715 increases the sensitivity (from 63% to 73%). However, the balanced accuracy increases only from 71% to 72%, and the specificity decreases from 80% to 72%.Conclusions/significanceC2/CFB significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the CFH-LOC387715 model is statistically significant

Spectrum of responses to intravitreal ganciclovir in the management of non AIDS related HCMV retinitis

Objective: To report and evaluate intravitreal ganciclovir injections in non-AIDS patients with human cytomegalovirus (HCMV) retinitis. Design: Retrospective chart review. Participants: Two SLE patients and one patient post chemotherapy for a non Hodgkin's lymphoma presented with myelosuppression and persistent cytomegalovirus retinitis despite systemic ganciclovir therapy. Methods: Patients were treated with 100 μL of intravitreal ganciclovir (4 mg/dL), initially given weekly. Systemic anti-CMV medication was stopped, and following quiescence, intravitreal injections were tapered and ultimately stopped based on therapeutic response. Patients were followed periodically for signs of recurrence. Results: Intravitreal ganciclovir was well tolerated and led to remission of the retinitis in 2 patients. One patient had persistent smouldering disease and reached quiescence using an intravitreal ganciclovir implant. Fluorescence-activated cell sorting analysis in one patient showed the presence of low CD4 and CD8 while treated with systemic ganciclovir, which improved with intravitreal treatment. In another, the low ratio was maintained against cytomegalovirus-specific antigens. Conclusions: Intravitreal ganciclovir injections should be considered as a treatment option in selected iatrogenically immunocompromised patients with HCMV retinitis. Responses may vary and will require an adjusted approach to treatment

Microscopic origin of the ‘0.7-anomaly’ in quantum point contacts

Quantum point contacts are narrow, one-dimensional constrictions usually patterned in a two-dimensional electron system, for example by applying voltages to local gates. The linear conductance of a point contact, when measured as function of its channel width, is quantized(1-3) in units of G(Q) = 2e(2)/h, where e is the electron charge and h is Planck's constant. However, the conductance also has an unexpected shoulder at similar to 0.7 G(Q), known as the '0.7-anomaly'(4-12), whose origin is still subject to debate(11-21). Proposed theoretical explanations have invoked spontaneous spin polarization(4,17), ferromagnetic spin coupling(19), the formation of a quasi-bound state leading to the Kondo effect(13,14), Wigner crystallization(16,20) and various treatments of inelastic scattering(18,21). However, explicit calculations that fully reproduce the various experimental observations in the regime of the 0.7-anomaly, including the zero-bias peak that typically accompanies it(6,9-11), are still lacking. Here we offer a detailed microscopic explanation for both the 0.7-anomaly and the zero-bias peak: their common origin is a smeared van Hove singularity in the local density of states at the bottom of the lowest one-dimensional subband of the point contact, which causes an anomalous enhancement in the Hartree potential barrier, the magnetic spin susceptibility and the inelastic scattering rate. We find good qualitative agreement between theoretical calculations and experimental results on the dependence of the conductance on gate voltage, magnetic field, temperature, source-drain voltage (including the zero-bias peak) and interaction strength. We also clarify how the low-energy scale governing the 0.7-anomaly depends on gate voltage and interactions. For low energies, we predict and observe Fermi-liquid behaviour similar to that associated with the Kondo effect in quantum dots(22). At high energies, however, the similarities between the 0.7-anomaly and the Kondo effect end