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Using a clinical pathway and education to reduce inappropriate prescribing of enoxaparin in patients with acute coronary syndromes: a controlled study.

AIMS: To evaluate efficacy of a pathway-based quality improvement intervention on appropriate prescribing of the low molecular weight heparin, enoxaparin, in patients with varying risk categories of acute coronary syndrome (ACS). METHODS: Rates of enoxaparin use retrospectively evaluated before and after pathway implementation at an intervention hospital were compared to concurrent control patients at a control hospital; both were community hospitals in south-east Queensland. The study population was a group of randomly selected patients (n = 439) admitted to study hospitals with a discharge diagnosis of chest pain, angina, or myocardial infarction, and stratified into high, intermediate, low-risk ACS or non-cardiac chest pain: 146 intervention patients (September-November 2003), 147 historical controls (August-December 2001) at the intervention hospital; 146 concurrent controls (September-November 2003) at the control hospital. Interventions were active implementation of a user-modified clinical pathway coupled with an iterative education programme to medical staff versus passive distribution of a similar pathway without user modification or targeted education. Outcome measures were rates of appropriate enoxaparin use in high-risk ACS patients and rates of inappropriate use in intermediate and low-risk patients. RESULTS: Appropriate use of enoxaparin in high-risk ACS patients was above 90% in all patient groups. Inappropriate use of enoxaparin was significantly reduced as a result of pathway use in intermediate risk (9% intervention patients vs 75% historical controls vs 45% concurrent controls) and low-risk patients (9% vs 62% vs 41%; P < 0.001 for all comparisons). Pathway use was associated with a 3.5-fold (95% CI: 1.3-9.1; P = 0.012) increase in appropriate use of enoxaparin across all patient groups. CONCLUSION: Active implementation of an acute chest pain pathway combined with continuous education reduced inappropriate use of enoxaparin in patients presenting with intermediate or low-risk ACS.

Angina, Unstable↗

Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles.

1. Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. 4. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Adolescent↗

Retrograde multiple and multifiber accessory pathway conduction in the Wolff-Parkinson-White syndrome: potential precipitating factor of atrial fibrillation.

INTRODUCTION: The determinants of susceptibility to atrial fibrillation (AF) and the existence of accessory pathway conduction have remained unidentified in the Wolff-Parkinson-White (WPW) syndrome. We tested the hypothesis that excitation inputs into the atrium over a retrograde multiple or multifiber accessory pathway during AV reentrant tachycardia (AVRT) could precipitate initiation of AF. METHODS AND RESULTS: Two hundred fifty consecutive patients with WPW syndrome underwent electrophysiologic study and radiofrequency catheter ablation. The patients were classified into two groups according to the study results: 29 with retrograde multiple or multifiber accessory pathway (MP) and 221 with retrograde single accessory pathway (SP). Compared with the SP patients, the MP patients showed a significantly higher incidence of clinical AF (MP vs SP: 19/29 vs 51/221, P < 0.01), induced AF (12/29 vs 32/221, P < 0.01), and initiated AF during ventricular pacing and AVRT (10/12 vs 17/32, P < 0.05). There were no differences between the two groups in incidence of clinical and induced AVRT (24/29 vs 200/221 and 25/29 vs 206/221, respectively), mean cycle length of induced AVRT, or electrophysiologic parameters of the accessory pathway. AF inducibility during AVRT or ventricular pacing was eliminated by partial ablation in 7 of 10 patients with MP. After total ablation, the incidence of induced AF was similar between the two groups (MP vs SP: 1/29 vs 11/221). CONCLUSION: The existence of a retrograde multiple or multifiber accessory pathway in patients with WPW syndrome is associated with a higher incidence of clinical and induced AF. Successful ablation of the retrograde multiple or multifiber accessory pathway can eliminate the induction of both AVRT and AF.

Adult↗

Role of the compact node and its posterior extension in normal atrioventricular nodal conduction, refractory, and dual pathway properties.

INTRODUCTION: The functional origin of AV nodal conduction, refractory, and dual pathway properties remains debated. The hypothesis that normal conduction and refractory properties of the compact node and its posterior nodal extension (PNE) play a critical role in the slow and the fast pathway, respectively, is tested with ablation lesions targeting these structures. METHODS AND RESULTS: A premature atrial stimulation protocol was performed before and after PNE ablation in six isolated rabbit heart preparations. Discrete (approximately 300 microm) histologically controlled PNE lesions amputated the AV nodal recovery curve from its left steep portion reflecting slow pathway conduction and prevented reentry without affecting the right smooth fast pathway portion of the curve. The ablation shortened A2H2max from 159 +/- 16 ms to 123 +/- 11 msec (P < 0.01) and prolonged the effective refractory period from 104 +/- 6 msec to 119 +/- 11 msec (P < 0.01) without affecting A2H2min (55 +/- 9 msec vs 55 +/- 8 msec; P = NS) and functional refractory period (174 +/- 7 msec vs 175 +/- 6 msec; P = NS). These results did not vary with the input reference used. In six other preparations, lesions applied to the compact node after PNE ablation shifted the fast pathway portion of the recovery curve to longer conduction times and prolonged the functional refractory period, suggesting a compact node involvement in the fast pathway. CONCLUSION: The normal AV nodal conduction and refractory properties reflect the net result of the interaction between a slow and a fast pathway, which primarily arise from the asymmetric properties of the PNE and compact node, respectively.

Animals↗

Multiple motor pathways to single smooth muscle cells in the ferret trachea.

1. We investigated the distribution and characteristics of motor pathways to individual smooth muscle cells activated by electrical stimulation of either, single nerves which enter the tracheal plexus (inlet nerves), or a longitudinal nerve trunk (LNT) located near the entrance of an inlet nerve into the plexus. Excitatory junction potentials (EJPs) were recorded using intracellular microelectrodes as an index of smooth muscle cell activation. In all experiments EJPs were completely blocked by tetrodotoxin and by atropine. 2. In smooth muscle fields located in the caudal direction from the point of inlet or LNT nerve stimulation, neural input decreased as a function of distance. There was evidence of a demarcated area innervated by neurons entering the plexus in one inlet nerve. In smooth muscle fields located in the rostral or transverse direction from the site of nerve stimulation, no such demarcated area could be identified. 3. Of the smooth muscle cells located within the innervated fields studied, 83-95% were activated following stimulation of a single inlet nerve or LNT. Evoked EJPs were similar in different innervated cells or units of electrically coupled cells located within the same 1 mm2 'field'. 4. There was overlapping cholinergic motor input to single smooth muscle cells originating from neurons present in different inlet nerves or different neurons present in the same inlet nerve or region of the LNT. Multiple small step increases in the voltage used to stimulate a LNT resulted in three or four step increases in EJP amplitudes. This gives a minimal value for the number of motor pathways that can be activated by neurons in a region of LNT leading to a single smooth muscle cell. 5. Motor pathways to smooth muscle cells located in caudal and rostral fields ran initially in the LNT and exited in proximity to the smooth muscle cell studied. 6. Motor pathways used in transmitting signals to smooth muscle cells to different areas of trachealis muscle varied in their sensitivity to hexamethonium or curare. EJPs evoked in fields located in the caudal direction from the stimulating electrode were abolished by these drugs. Muscle cells located in different rostral fields showed EJPs that were either sensitive or resistant to these drugs. 7. The rostral hexamethonium-resistant pathway ran initially in the LNT but it exited from the LNT several millimetres before reaching the level of the smooth muscle field innervated. This pathway followed stimulation frequencies up to 25 Hz. The final neuron in this pathway released acetylcholine and evoked EJPs were entirely inhibited by atropine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation.

The effect of meningococcal cell-associated sialic acid on activation of the human alternative complement pathway was examined by using a quantitative fluorescence immunoassay to assess alternative pathway-mediated C3 binding to a group B strain of Neisseria meningitidis from which graded amounts of sialic acid had been removed with neuraminidase. Using human serum absorbed with strain B16B6 (B:2a:L2,3) and chelated with 10 mM MgCl2 and 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, we found an increase in the amount of C3 bound by enzymatically desialylated B16B6 organisms over the amount bound by fully sialylated organisms. This increase was proportional to the amount of sialic acid cleaved from the bacteria. Enhanced C3 binding was accompanied by an increase in factor B deposition. A sialic acid-deficient mutant of strain B16B6, designated 2T4-1, bound C3 via the alternative pathway at a level equivalent to that bound by wild-type meningococci from which 88% of the sialic acid had been removed. Strain B16B6 was resistant to the alternative pathway-mediated bactericidal activity of both absorbed and hypogammaglobulinemic human sera, whereas noncapsular variant 2T4-1 was sensitive to these sera. The addition of purified immune immunoglobulin M (IgM) and IgG significantly increased the alternative pathway-mediated killing of strain B16B6 organisms. IgM mediated increased bactericidal activity without an increase in C3 or factor B deposition. In contrast, the IgG-mediated killing was associated with increased binding of C3 and factor B to the organisms. Absorption studies showed that the IgM bound to the sialic acid capsule, whereas the IgG bound to noncapsular surface antigens. We conclude from these results that the group B meningococcal sialic acid capsule inhibits activation of the alternative pathway in the nonimmune host and that both IgM and IgG, although specific for different surface antigens, are capable of augmenting the alternative pathway-mediated killing of group B meningococci.

Antibodies, Bacterial↗

Mannan-specific immunoglobulin G antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway.

Candida albicans activates the classical and alternative complement pathways, leading to deposition of opsonic complement fragments on the cell surface. Our previous studies found that antimannan immunoglobulin G (IgG) in normal human serum (NHS) allows C. albicans to initiate the classical pathway. The purpose of this study was to determine whether antimannan IgG also plays a role in initiation of the alternative pathway. Pooled NHS was rendered free of classical pathway activity by chelation of serum Ca2+ with EGTA alone or in combination with immunoaffinity removal of antimannan antibodies. Kinetic analysis revealed a 6-min lag in detection of C3 binding to C. albicans incubated in EGTA-chelated NHS, compared to a 12-min lag in NHS that was both EGTA chelated and mannan absorbed. The 12-min lag was shortened to 6 min by addition of affinity-purified antimannan IgG. The accelerating effect of antimannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six purified proteins of the alternative pathway. Both Fab and F(ab')2 fragments of antimannan IgG facilitated alternative pathway initiation in a manner similar to that observed with intact antibody. Immunofluorescence analysis showed that addition of antimannan IgG to EGTA-chelated and mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. Thus, antimannan IgG antibodies play an important regulatory role in interactions between the host complement system and C. albicans.

Antibodies, Fungal↗

Biosynthesis and biosynthetic pathways of pentoses in Escherichia coli.

Sable, Henry Z. (Western Reserve University, Cleveland, Ohio) and Elayne E. Cassisi. Biosynthesis and biosynthetic pathways of pentoses in Escherichia coli. J. Bacteriol. 84:1169-1172. 1962.-Resting glucose-adapted Escherichia coli supplied with glucose continues to synthesize pentose by the oxidative pathway characteristic of logarithmically growing glucose-adapted cells. This behavior is unlike that of acetate-adapted resting E. coli supplied with glucose, which continues to synthesize most of its pentose by the nonoxidative pathway characteristic of acetate-adapted cells. When infected with bacteriophage T2H, E. coli continues to use the oxidative pathway predominantly. This finding is in contrast to reports that infection with T6r+ bacteriophage increases the participation of a nonoxidative pathway. Resting glucose-adapted E. coli supplied with acetate-1-C(14) as sole carbon source synthesizes pentose by a pathway or pathways which cannot be assessed completely by methods previously developed (which are based on the relative labeling of C-1, C-2, and C-3 of the pentose) but which is most probably predominantly nonoxidative.

Acetates↗

Training-induced adaptive plasticity in human somatosensory reflex pathways.

This paper reviews evidence supporting adaptive plasticity in muscle and cutaneous afferent reflex pathways induced by training and rehabilitative interventions. The perspective is advanced that the behavioral and functional relevance of any intervention and the reflex pathway under study should be considered when evaluating both adaptation and transfer. A cornerstone of this concept can be found in acute task-dependent reflex modulation. Because the nervous system allows the expression of a given reflex according to the motor task, an attempt to evaluate the training adaptation should also be evoked under the same conditions as training bearing in mind the functional role of the pathway under study. Within this framework, considerable evidence supports extensive adaptive plasticity in human muscle afferent pathways in the form of operant conditioning, strength training, skill training, and locomotor training or retraining. Directly comparable evidence for chronic adaptation in cutaneous reflex pathways is lacking. However, activity-dependent plasticity in cutaneous pathways is documented particularly in approaches to neurological rehabilitation. Overall, the adaptive range for human muscle afferent reflexes appears bidirectional (that is, increased or reduced amplitudes) and on the order of 25-50%. The adaptive range for cutaneous pathways is currently uncertain.

Action Potentials↗

Contextual modulation of olivocochlear pathway effects on loud sound-induced cochlear hearing desensitization.

This study shows that the cochlear hearing losses [temporary threshold shifts (TTSs)] induced by traumatic sound and the effect of olivocochlear (OC) pathways to the cochlea on these hearing losses depend on the context of the sound. Background atraumatic white noise (WN) has been shown to 1) exacerbate loud-pure-tone-induced TTSs, and 2) promote the modulation of TTSs by the uncrossed OC (UOC) pathways additional to the action on TTSs, elicited by binaural loud tones themselves, by the crossed OC (COC) pathway. Here the same atraumatic WN reduced TTSs caused by loud narrow band sound. It also reduced TTS modulation by OC pathways. The UOC no longer exerted any effects on TTSs, and COC effects were significantly reduced in two discrete frequency bands: low frequencies within the narrow band ("within-band" frequencies) and high frequencies outside the band ("high-side" frequencies). COC effects were unchanged at high frequencies within the band. Despite these reductions in OC effects, because the WN itself reduced TTSs, the total effect of OC pathways and background WN now produced larger TTS reductions, especially at higher frequencies. Thus the modulatory effects of the OC pathways on TTSs depend on how background WN modulates cochlear state. It is postulated that the WN background and the OC pathways both modulate TTSs by acting on the outer hair cells, in a way that promotes the reduction of TTSs caused by the narrow band sound trauma. This joint promotion of a protective end-effect on TTSs to narrow band sound trauma contrasts against the effects seen with pure tone trauma where the same background WN exacerbated TTSs at high-side frequencies.

Acoustic Stimulation↗

Relative roles of the S cell network and parallel interneuronal pathways in the whole-body shortening reflex of the medicinal leech.

The whole-body shortening reflex of the medicinal leech Hirudo medicinalis is a withdrawal response produced by anterior mechanical stimuli. The interneuronal pathways underlying this reflex consist of the S cell network (a chain of electrically coupled interneurons) and a set of other, parallel pathways. We used a variety of techniques to characterize these interneuronal pathways further, including intracellular stimulation of the S cell network, photoablation of the S cell axon, and selective lesions of particular connectives (the axon bundles that link adjacent ganglia in the leech nerve cord). These experiments demonstrated that the S cell network is neither sufficient nor necessary for the production of the shortening reflex. The axons of the parallel pathways were localized to the lateral connectives (whereas the S cell axon runs through the medial connective). We used physiological techniques to show that the axons of the parallel pathways have a larger diameter in the anterior connective and to demonstrate that the parallel pathways are activated selectively by anterior mechanosensory stimuli. We also presented correlative evidence that the parallel pathways, along with activating motor neurons during shortening, are responsible for inhibiting a higher-order "command-like" interneuron in the neuronal circuit for swimming, thus playing a role in the behavioral choice between swimming and shortening.

Animals↗

Relating MRI changes to motor deficit after ischemic stroke by segmentation of functional motor pathways.

BACKGROUND AND PURPOSE: Infarct size on T2-weighted MRI correlates only modestly with outcome, particularly for small strokes. This may be largely because of differences in the locations of infarcts and consequently in the functional pathways that are damaged. To test this hypothesis quantitatively, we developed a "mask" of the corticospinal pathway to determine whether the extent of stroke intersection with the pathway would be more closely related to clinical motor deficit and axonal injury in the descending motor pathways than total stroke lesion volume. METHODS: Eighteen patients were studied > or =1 month after first ischemic stroke that caused a motor deficit by use of brain T2-weighted imaging, MR spectroscopic (MRS) measurements of the neuronal marker compound N-acetyl aspartate in the posterior limb of the internal capsule, and motor impairment and disability measures. A corticospinal mask based on neuroanatomic landmarks was generated from a subset of the MRI data. The maximum proportion of the cross-sectional area of this mask occupied by stroke was determined for each patient after all brain images were transformed into a common stereotaxic brain space. RESULTS: There was a significant linear relationship between the maximum proportional cross-sectional area of the corticospinal mask occupied by stroke and motor deficit (r(2)=0.82, P<0.001), whereas the relationship between the total stroke volume and motor deficit was better described by a cubic curve (r(2)=0.76, P<0.001). Inspection of the data plots showed that the total stroke volume discriminated poorly between smaller strokes with regard to the extent of associated motor deficit, whereas the maximum proportion of the mask cross-sectional area occupied by stroke appeared to be a more discriminatory marker of motor deficit and also N-acetyl aspartate reduction. CONCLUSIONS: Segmentation of functional motor pathways on MRI allows estimation of the extent of damage specifically to that pathway by the stroke lesion. The extent of stroke intersection with the motor pathways was more linearly related to the magnitude of motor deficit than total lesion volume and appeared to be a better discriminator between small strokes with regard to motor deficit. This emphasizes the importance of the anatomic relationship of the infarct to local structures in determining functional impairment. Prospective studies are necessary to assess whether this approach would allow improved early estimation of prognosis after stroke.

Adult↗

Rod-cone interactions assessed in inferred magnocellular and parvocellular postreceptoral pathways.

Interactions between receptor-isolating rod and long (L)- or middle (M)-wavelength-sensitive cone modulations at 2 Hz and 10 Hz were analyzed in terms of underlying inferred magnocellular (MC) and parvocellular (PC) postreceptoral pathways. Stimuli originated from a colorimeter with 4 primaries in both the center and surround fields. The first experiment employed a phase paradigm in which the thresholds for mixed rod and cone modulations were measured as a function of relative phase. The amplitudes of the rod and cone modulations, equated in threshold units, were varied in tandem. In the second experiment, thresholds for mixed rod and cone modulations were measured as a function of the ratio of the rod and cone modulation amplitudes for 2 fixed phase offsets. Both experiments yielded similar interpretations of rod and L- (or M-) cone interactions. At 1 and 10 troland (td), rod and L- (or M-) cone interactions varied depending on the postreceptoral pathways underlying the detection. When cone thresholds were mediated by the inferred MC pathway, rod and cone thresholds showed almost linear summation. When cone thresholds were mediated by the inferred PC pathway, rod and cone thresholds showed probability summation. Assuming that signals within the same pathway follow linear summation, and signals traveling in different pathways follow probability summation, we concluded that the rod thresholds were mediated by the inferred MC pathway for both the 2-Hz and 10-Hz conditions.

Contrast Sensitivity↗

Nutrition support clinical pathways.

With growing concerns over cost containment, hospitals are using clinical pathways to standardize health care and reduce costs. Clinical pathways designate the actions and services that patients should receive at specified time intervals throughout the hospital stay. Although most clinical pathways have been created for specific diseases or diagnoses, the nutrition support team at Tallahassee Memorial Regional Medical Center has developed clinical pathways for enteral and parenteral therapies. These pathways allow the team to track patient outcomes related to nutrition and to document variances when provisions fall outside the pathways. Variances are tallied on a quarterly basis and reported to the hospital Nutrition Support Committee. As data collection continues, trends emerge that guide the team to take appropriate corrective actions. Patient care is continuosly improved by incorporating these corrective actions into the pathways.

Cost Control↗

An evidence-based clinical pathway for bronchiolitis safely reduces antibiotic overuse.

The overuse of antibiotics in the management of bronchiolitis is widely known, yet physician practice has been slow to change. We report here on the success of a clinical pathway in reducing antibiotic overuse in the inpatient management of bronchiolitis. The charts of 181 children admitted for bronchiolitis were reviewed to determine whether antibiotic use was reduced in patients managed using a clinical pathway compared with a matched group of patients managed without use of the pathway (non-pathway group). Only 9% of the pathway patients received antibiotics compared with 27% of the nonpathway group. No negative effects were seen on other quality measures including unplanned return for care. Furthermore, for patients managed using the clinical pathway, cost and length of stay were significantly reduced. Overall, the study suggests that implementation of a clinical pathway may be an effective means to change physician practice and reduce the unnecessary use of antibiotics, while maintaining or improving other aspects of quality of care.

Anti-Bacterial Agents↗

The role of a clinical pathway in curtailing unnecessary investigations in children with gastroenteritis.

Clinical pathways are useful tools in improving the quality of care of patients treated in hospitals. Gastroenteritis is a short, self-limiting, but common illness of childhood associated with significant costs to the community. The authors assessed the impact of a clinical pathway on investigation ordering in children with gastroenteritis. A retrospective analysis of 2 cohorts of children was performed before (n=1498) and after (n=1252) the introduction of a clinical pathway. Children admitted to hospital with a diagnosis of gastroenteritis were assessed as to the type of pathology tests ordered. Further outcomes measured were rates of admission, emergency department presentations, average length of stay, and direct costs. Subset analysis was undertaken on the initial cohort of patients who had a full blood count as part of their initial assessment. Full blood count was more likely to be performed prior to the introduction of the pathway(77.1%) than after pathway introduction (66.8%; P<.004). Urine microscopy and culture also was significantly decreased from 56.3% to 40.4% (P<.0005). Median patient costs were reduced from $1228 to $752 following pathway introduction (P<.0001); however, rates of admission were increased from 18.6% to 28.8% (P<.0001). Length of stay decreased but was not statistically significant. Full blood count results in the subset analysis revealed that the measurement of a full blood count had no impact on management. Thus, a clinical pathway contributed to more rational ordering of pathology tests and lowered the costs to a hospital of caring for patients with this common illness.

Child, Preschool↗

Interleukin-6 related signaling pathways as the intersection between chronic diseases and sepsis.

Sepsis is associated with immune dysregulated and organ dysfunction due to severe infection. Clinicians aim to restore organ function, rather than prevent diseases that are prone to sepsis, resulting in high mortality and a heavy public health burden. Some chronic diseases can induce sepsis through inflammation cascade reaction and Cytokine Storm (CS). Interleukin (IL)-6, the core of CS, and its related signaling pathways have been considered as contributors to sepsis. Therefore, it is important to study the relationship between IL-6 and its related pathways in sepsis-related chronic diseases. This review generalized the mechanism of sepsis-related chronic diseases via IL-6 related pathways with the purpose to take rational management for these diseases. IL-6 related signaling pathways were sought in Kyoto Encyclopedia of Genes and Genomes (KEGG), and retrieved protein-protein interaction in the Search for Interaction Genes tool (STRING). In PubMed and Google Scholar, the studies were searched out, which correlating to IL-6 related pathways and associating with the pathological process of sepsis. Focused on the interactions of sepsis and IL-6 related pathways, some chronic diseases have been studied for association with sepsis, containing insulin resistance, Alcoholic liver disease (ALD), Alzheimer disease (AD), and atherosclerosis. This article summarized the inflammatory mechanisms of IL-6 cross-talked with other mediators of some chronic diseases in vitro, animal models, and human experiments, leading to the activation of pathways and accelerating the progression of sepsis. The clinicians should be highlight to this kind of diseases and more clinical trials are needed to provide more reliable theoretical basis for health policy formulation.

Humans↗

Introducing an integrated care pathway for the last days of life.

Integrated care pathways (ICPs) are multiprofessional documents designed to enable the implementation of evidence-based care and support the practical delivery of clinical governance. However, the implementation of care pathways is resource intensive and few evaluations have been conducted with respect to these areas or to the efficacy of care pathways to change practice and improve outcomes in care. This project sought to address these issues and the report outlines the approach taken by a palliative care team in South Wales, UK, to implement a care pathway for the dying throughout a district general hospital and six community hospitals. Dying can be a complex area of care and changing practice can be challenging, therefore a PRINCE Project management approach was taken and a full-time project nurse employed for the life of the project. This paper describes the strategies used to approach implementing a care pathway and provides a template for other teams who may embark on similar projects. At the end of the project, the care pathway was successfully implemented and provided demonstrable outcomes of care for those dying from cancer and nonmalignant diseases. Strikingly, a large number of patients dying from nonmalignant disease were cared for via the pathway, which was not expected.

Analysis of Variance↗