The cost of moderate and severe COPD exacerbations to the Canadian healthcare system

SummaryBackgroundThe cost of exacerbations in chronic obstructive pulmonary disease (COPD) has not been well studied. The aim of this study was to identify and quantify the (average) cost of moderate and severe exacerbations (ME and SE, respectively) from a Canadian perspective.MethodsResources used during ME and SE were identified in a year long prospective, observational study (Resource Utilization Study In COPD (RUSIC)). The units of analysis were ME and SE. Unit costs (2006$CAN), based on provincial, hospital and published sources, were applied to resources. The overall cost per ME and SE were calculated. The population burden of exacerbations was also calculated.ResultsAmong study participants (N=609, aged 68.6±9.4 years, 58.3$126 (N=574) and $515 (N=105), respectively. The average overall cost of a ME was$641. For SEs, the average hospital stay was 10.0 days. The overall mean costs of outpatient, ED and hospitalization services for SE were $114 (N=44),$774 (N=140) and $8669 (N=151), respectively. The average overall cost of a SE was$9557.ConclusionThe economic burden associated with MEs and especially SEs, in Canada, is considerable and likely has a substantial impact on healthcare costs. The overall burden of exacerbations has been estimated in the range of $646 million to$736 million per annum

Recovery kinetics of short-term depression of GABAergic and glutamatergic synapses at layer 2/3 pyramidal cells in the mouse barrel cortex

IntroductionShort-term synaptic plasticity (STP) is a widespread mechanism underlying activity-dependent modifications of cortical networks.MethodsTo investigate how STP influences excitatory and inhibitory synapses in layer 2/3 of mouse barrel cortex, we combined whole-cell patch-clamp recordings from visually identified pyramidal neurons (PyrN) and parvalbumin-positive interneurons (PV-IN) of cortical layer 2/3 in acute slices with electrical stimulation of afferent fibers in layer 4 and optogenetic activation of PV-IN.ResultsThese experiments revealed that electrical burst stimulation (10 pulses at 10 Hz) of layer 4 afferents to layer 2/3 neurons induced comparable short-term depression (STD) of glutamatergic postsynaptic currents (PSCs) in PyrN and in PV-IN, while disynaptic GABAergic PSCs in PyrN showed a stronger depression. Burst-induced depression of glutamatergic PSCs decayed within <4 s, while the decay of GABAergic PSCs required >11 s. Optogenetically-induced GABAergic PSCs in PyrN also demonstrated STD after burst stimulation, with a decay of >11 s. Excitatory postsynaptic potentials (EPSPs) in PyrN were unaffected after electrical burst stimulation, while a selective optogenetic STD of GABAergic synapses caused a transient increase of electrically evoked EPSPs in PyrN.DiscussionIn summary, these results demonstrate substantial short-term plasticity at all synapses investigated and suggest that the prominent STD observed in GABAergic synapses can moderate the functional efficacy of glutamatergic STD after repetitive synaptic stimulations. This mechanism may contribute to a reliable information flow toward the integrative layer 2/3 for complex time-varying sensory stimuli

The psychosocial cost burden of cancer : A systematic literature review

BACKGROUND AND OBJECTIVE: Psychosocial costs, or quality of life costs, account for psychological distress, pain, suffering and other negative experiences associated with cancer. They contribute to the overall economic burden of cancer that patients experience. But this category of costs remains poorly understood. This hinders opportunities to make the best cancer control policy decisions. This study explored the psychosocial cost burden associated with cancer, how studies measure psychosocial costs and the impact of this burden. METHODS: A systematic literature review of academic and grey literature published from 2008 to 2018 was conducted by searching electronic databases, guided by the Institute of Medicine's conceptualization of psychosocial burden. Results were analyzed using a narrative synthesis and a weighted proportion of populations affected was calculated. Study quality was assessed using the Ottawa-Newcastle instrument. RESULTS: A total of 25 studies were included. There was variation in how psychosocial costs were conceptualized and an inconsistent approach to measurement. Most studies measured social dimensions and focused on the financial consequences of paying for care. Fewer studies assessed costs associated with the other domains of this burden, including psychological, physical, and spiritual dimensions. Fourty-four percent of cancer populations studied were impacted by psychosocial costs and this varied by disease site (38%-71%). Two studies monetized the psychosocial cost burden, estimating a lifetime cost per case ranging from CAD$427753 to CAD$528769. Studies were of varying quality; 60% of cross-sectional studies had a high risk of bias. CONCLUSIONS: Consistency in approach to measurement would help to elevate this issue for researchers and decision makers. At two-thirds of the total economic burden of cancer, economic evaluations should account for psychosocial costs to better inform decision-making. More support is needed to address the psychosocial cost burden faced by patients and their families

Cost-Effectiveness of Adding Cetuximab to Platinum-Based Chemotherapy for First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer

To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) from the perspective of the Canadian public healthcare system.We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%.In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER) of$386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab.The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy

Health state utilities of a population of Nigerian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Establishment of the health impact of hypertension on quality of life of Nigerians is a step towards controlling the disease. The study aimed to provide a Nigerian specific reference list of utility scores of hypertensive patients with various interacting conditions.</p> <p>Findings</p> <p>An interviewer-based, cross-sectional study was conducted using hypertensive patients in two purposively selected tertiary hospitals located in South-Eastern Nigeria. Health Utility Index Mark 3 (HUI3) was used.</p> <p>A total of 384 participants with either hypertension alone or with hypertension-associated complications were interviewed in the two tertiary hospitals.</p> <p>The overall mean utility score was 0.35 +/- 0.42. Patients with hypertension alone had the highest overall mean utility score (0.57 +/- 0.29) while hypertensive patients with stroke had the lowest overall mean score (0.04 +/- 0.36). Being a male, increase in age and mean arterial blood pressure, emergency visit and loss of work due to illness were associated with significant decrease in overall utility scores.</p> <p>Conclusions</p> <p>This study presented a reference for health state utilities of a population of Nigerian hypertensive patients.</p

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths