Post-Operative Pain Scores and Level of Regional Anesthesia Expertise: Using Clinical Outcomes to Assess Procedural Proficiency

Background and Objectives: Peripheral nerve blockade requires regional anesthesia skills that trainees learn in several formats. Technical proficiency has shifted from a quota to comprehensive procedural evaluation. Successful nerve blockade is the clinical endpoint validating proficiency but patient, technical and procedural factors influence this result. The purpose of this study was to determine if procedural expertise for sciatic nerve blockade influenced postoperative pain scores and opioid requirements and if patient factors, technique and repetition influenced this outcome. Method: Sciatic nerve blockade by nerve stimulation and ultrasound guidance and training level of the resident performing the procedure were recorded. Patient obesity, trauma, chronic pain, opioid use and preoperative pain scores were compared to post-procedure pain scores and opioid analgesic requirements. Results: 102 patients received sciatic nerve blockade from 47 trainees over a 36 month interval. A significant relation between training level and improved pain scores was not demonstrated but transition from nerve stimulation to ultrasound guidance lowered scores in all groups. Nerve blockade failure was frequent with chronic opioid use and trauma. Conclusion: Analgesic outcomes should be an integral part of assessment of proficiency in regional anesthesia techniques. Evaluating outcomes of procedures throughout training will longitudinally assess technical expertise.

Clinical outcomes from skin screening clinics within a community-based melanoma screening program

Background : Within a randomized trial of population screening for melanoma, primary care physicians conducted whole-body skin examinations and referred all patients with suspect lesions to their own doctor for further treatment. Objective: Our aim was to describe characteristics of skin screening participants, clinical screening diagnoses, management following referral, and specificity and yield of screening examinations. Methods: Information collected from consent forms, referral forms, and histopathological reports of lesions that had been excised or undergone biopsy was analyzed by means of descriptive statistics. Results: A total of 16,383 whole-body skin examinations resulted in 2302 referrals (14.1% overall; 15.5% men, 18.2% >= 50 years of age) for 4129 suspect lesions (including 222 suspected melanoma, 1101 suspected basal cell carcinomas [BCCs], 265 suspected squamous cell carcinomas [SCCs]). Histopathologic results were available for 94.8% of 1417 lesions excised and confirmed 33 melanomas (23 in men; 24 in participants ? 50 years of age), 259 BCCs, and 97 SCCs. The probability of detecting skin cancer of any type within the program was 2.4%. The estimated specificity of whole-body skin examinations for melanoma was 86.1% (95% confidence interval = 85.6-86.6). The positive predictive value (number of confirmed/number of lesions excised or biopsied x 100) for melanoma was 2.5%, 19.3% for BCC, and 7.2% for SCC (overall positive predictive value for skin cancer, 28.9%). Limitations: Follow-up of participants with a negative screening examination has not been conducted for the present investigation. Conclusions: The rate of skin cancer detected per 100 patients screened was higher than previously reported and men and attendees older than 50 years more frequently received a referral and diagnosis of melanoma. The specificity for detection of melanoma through whole-body skin examination by a primary care physician was comparable to that of other screening tests, including mammography.

Implementation of Triple P-Positive Parenting Program in Hong Kong: Predictors of programme completion and clinical outcomes

This study examined the effectiveness of the Triple P-Positive Parenting Program in a government child health service delivery context with Chinese parents in Hong Kong. Specifically, the study sought to identify pre-intervention variables that might predict programme outcomes such as, level of clinical improvement and programme completion. Participants were 661 parents of pre-school and primary aged children participating in a group version of the Triple P-Positive Parenting Program. There were significant decreases in disruptive child behaviours, levels of parenting stress, general stress and anxiety and an increase in parenting sense of competence. Greater change in reports of child behaviour problems was related to lower levels of family income, new immigrant family status, and higher pre-intervention levels of parenting stress. The present study provides a profile of parents who are most likely to benefit from parent training programmes.

Clinical outcomes after implantation of a new hydrophobic acrylic toric IOL during routine cataract surgery

PURPOSE: To assess the clinical outcomes after implantation of a new hydrophobic acrylic toric intraocular lens (IOL) to correct preexisting corneal astigmatism in patients having routine cataract surgery. SETTING: Four hospital eye clinics throughout Europe. DESIGN: Cohort study. METHODS: This study included eyes with at least 0.75 diopter (D) of preexisting corneal astigmatism having routine cataract surgery. Phacoemulsification was performed followed by insertion and alignment of a Tecnis toric IOL. Patients were examined 4 to 8 weeks postoperatively; uncorrected distance visual acuity (UDVA), corrected distance visual acuity, manifest refraction, and keratometry were measured. Individual patient satisfaction with uncorrected vision and the surgeon’s assessment of ease of handling and performance of the IOL were also documented. The cylinder axis of the toric IOL was determined by dilated slitlamp examination. RESULTS: The study enrolled 67 eyes of 60 patients. Four to 8 weeks postoperatively, the mean UDVA was 0.15 logMAR G 0.17 (SD) and the UDVA was 20/40 or better in 88% of eyes. The mean refractive cylinder decreased significantly postoperatively, from -1.91 +/- 1.07 D to -0.67 +/- 0.54 D. No significant change in keratometric cylinder was observed. The mean absolute IOL misalignment from the intended axis was 3.4 degrees (range 0 to 12 degrees). The good UDVA resulted in high levels of patient satisfaction. CONCLUSION: Implantation of the new toric IOL was an effective, safe, and predictable method to manage corneal astigmatism in patients having routine cataract surgery.

Strategies for treating chronic HCV infection in patients with cirrhosis: latest evidence and clinical outcomes.

The burden of chronic hepatitis C virus (HCV) infection is significant and growing. HCV is considered one of the leading causes of liver disease worldwide and the leading cause of liver transplantation globally. While those infected is estimated in the hundreds of millions, this is likely an underestimation because of the indolent nature of this disease when first contracted. Approximately 20% of patients with HCV infection will progress to advanced fibrosis and cirrhosis. Those that do are at risk of decompensated liver disease including GI bleeding, encephalopathy, severe lab abnormalities, and hepatocellular carcinoma. Those individuals with advanced fibrosis and cirrhosis have historically been difficult to treat. The backbone of previous HCV regimens was interferon (IFN). The outcomes for IFN based regimens were poor and resulted in increased adverse events among those with advanced fibrosis and cirrhosis. Now, in the era of new direct acting antiviral (DAA's) medications, there is hope for curing chronic HCV in everyone, including those with advanced fibrosis and cirrhosis. This article provides a review on the most up to date data on the use of DAA's in patients with advanced fibrosis and cirrhosis. We are at a point where HCV could be truly eradicated, but to do so will require ensuring there are effective and safe treatments for those with advanced fibrosis and cirrhosis.

XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments.

Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding. Recent studies have highlighted the importance of IRE1alpha and X box binding protein 1 (XBP1), key members of this pathway, in normal B-plasma cell development. We have determined the gene expression levels of IRE1alpha, XBP1, XBP1UNSPLICED (XBP1u), and XBP1SPLICED (XBP1s) in a series of patients with myeloma and correlated findings with clinical outcome. We show that IRE1alpha and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival. XBP1s is an independent prognostic marker and can be used with beta2 microglobulin and t(4;14) to identify a group of patients with a poor outcome. Furthermore, we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios. This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response.

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

BACKGROUND: -There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease (RHD) or information on their predictors. We report the two year follow-up of individuals with RHD from 14 low and middle income countries in Africa and Asia.

METHODS: -Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for two years to assess mortality, congestive heart failure (CHF), stroke or transient ischemic attack (TIA), recurrent acute rheumatic fever (ARF), and infective endocarditis (IE).

RESULTS: -Vital status at 24 months was known for 2960 (88.5%) patients. Two thirds were female. Although patients were young (median age 28 years, interquartile range 18 to 40), the two year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.80-3.11), CHF (HR 2.16, 95% CI 1.70-2.72), New York Heart Association functional class III/IV (HR 1.67, 95% CI 1.32-2.10), atrial fibrillation (AF) (HR 1.40, 95% CI 1.10-1.78) and older age (HR 1.02, 95% CI 1.01-1.02 per year increase) at enrolment. Post-primary education (HR 0.67, 95% CI 0.54-0.85) and female sex (HR 0.65, 95%CI 0.52-0.80) were associated with lower risk of death. 204 (6.9%) had new CHF (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or TIA (8.45/1000 patient-years), 19 (0.6%) had ARF (3.49/1000 patient-years), and 20 (0.7%) had IE (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/TIA or systemic embolism. Patients from low and lower-middle income countries had significantly higher age- and sex-adjusted mortality compared to patients from upper-middle income countries. Valve surgery was significantly more common in upper-middle income than in lower-middle- or low-income countries.

CONCLUSIONS: -Patients with clinical RHD have high mortality and morbidity despite being young; those from low and lower-middle income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and treatment of clinical RHD are required to improve outcomes.

Usefulness of clinical observations and blood chemistry values for predicting clinical outcomes in dairy goats with pregnancy toxaemia

Background Pregnancy toxaemia (PT) is a disease that affects pregnant goats during their last month of gestation and is characterized by a high case fatality rate. This study involved 32 does maintained on a commercial dairy goat farm that were diagnosed with PT. A physical examination was performed on and haematology parameters obtained from each doe, at the time of diagnosis. The data from the 24 PT goats that died was compared with the corresponding data from the 8 PT goats that survived. Results Polypnea, swollen limbs, anorexia with absence of ruminal motility, recumbency, nervous signs and drooping ears were the most frequently observed clinical manifestations. Nineteen out of 21 recumbent goats died. Sixteen out of 17 goats with anorexia and absence of ruminal motility died. Mean beta-hydroxybutyric acid (BHBA) values in the goats that died were not significantly different from those in goats that survived. The blood values for pH and pCO2 (p < 0.005) as well as for HCO3 −, BE and K+ (p < 0.001) were significantly lower in the goats that died than in those that survived. Conclusions The clinical signs most indicative of a poor prognosis are anorexia with absence of ruminal motility and recumbency. Among the blood parameters to be considered, hypokalaemia and metabolic acidosis are the most relevant. Goats with PT have a high mortality and their condition can deteriorate very fast. Based on the authors’s experience, a good strategy to minimize the economic losses caused by PT is to focus on the offspring survival rate since an early decision (induction of kidding or caesarian surgery) can increase the number of alive kids.

Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

Background: Patients with lupus nephritis could progress to endstage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis.

Antiplatelet therapy and clinical outcomes in cardiovascular diseases

Cardiovascular diseases (CVD) is a leading cause of death in the world. Despite effective treatment regimens for ischaemic heart disease (IHD) and ischaemic stroke, mortality and recurrence rates remain high. Antiplatelet therapy is on effective treatment and reduces the risk of recurrent heart attack and stroke. Nevertheless, there are patients who stopped or interrupted their antiplatelet therapy for certain reasons or some patients may be resistant or poor responders to antiplatelet therapy. Furthermore, there is evidence of rebound effect in platelet activity after antiplatelet cessation and this may associate with increased risk of cardiovascular event. This thesis is divided into five main chapters (chapters 3 to 7) which attempt to provide data to help resolve the uncertainty. Chapter 1 highlights the background of cardiovascular diseases and the global burden of cardiovascular and cerebrovascular diseases. The metabolism of platelets, antiplatelet therapy and current antiplatelet therapy guidelines are described, followed by discussion of the risk of cardiovascular event and changes in antiplatelet therapy. Chapter 2 describes the data source from Virtual International Stroke Trial Archive (VISTA) and National Health Service Greater Glasgow and Clyde (NHSGGC) Safe Haven, followed by definition of outcome measures. In chapter 3, Virtual International Stroke Trial Archive (VISTA) data was examined to test whether continue with the same antiplatelet therapy or changing to a new antiplatelet regimen reduces the risk of subsequent events in patients who experience a stroke whilst taking antiplatelet therapy. The findings indicate that subjects who switch to a new antiplatelet regimen after stroke did not have a lower early recurrence rate than subjects who continued with the same antiplatelet therapy. Observations on bleeding complications were similar in both groups. However, changing antiplatelet regimen after stroke was associated with more favourable functional outcome across a full scale modified Rankin Scale (mRS) at 90 days. In chapter 4, association between early or later initiation of antiplatelet with a recurrent ischaemic stroke and bleeding complications was assessed using VISTA data. The findings indicate that there was no association between a recurrent ischaemic stroke and timing of initiation of antiplatelet drug after stroke. However, early initiation was associated with increased risk of bleeding. In terms of functional outcomes, this study demonstrated that the mid-time and late initiation of antiplatelet therapy after acute stroke are associated with better functional outcomes compared with early initiation. In chapter 5, a nested case-control study was performed to explore the rate of antiplatelet cessation and interruption in a sample of patients with recent ischaemic stroke and to assess the risk of cardiovascular events associated with cessation and interruption of antiplatelet. It was found that there was no increased risk of cardiovascular event among patients who had early cessation or interrupted/stopped antiplatelet therapy within 90 days following acute ischaemic stroke. In chapter 6, the incidence and predictors of cardiovascular events after DAPT cessation were evaluated. The incidence of cardiovascular event while taking DAPT and following discontinuation of DAPT was 15.7% and 16.7% respectively. This study found that increasing age was associated with an increased risk of cardiovascular event, whereas, revascularization-treated patients and longer duration of DAPT, were each associated with a decreased risk. The duration of DAPT six months and less was associated a significantly higher risk for cardiovascular event. In chapter 7, an untargeted metabolomics analysis was performed while on DAPT (aspirin plus ticagrelor) and once they stopped ticagrelor to identify metabolite changes associated with cardiovascular events after stopping DAPT. Ten ACS patients were recruited in this study and data were analysed for seven patients. Three hundred eleven putative metabolites were identified. This study found 16 putative metabolites significantly altered following ticagrelor cessation. Of these, seven metabolites were from lipid pathway and down-regulated some up to 3-fold. On the other hand, adenosine, from nucleotide metabolism was upregulated up to 2.6-fold. It concluded that there are changes in numerous pathways following DAPT discontinuation and whether these changes differ in patients who have cardiovascular event after stopping DAPT warrant further investigation. In chapter 8, a summary of the findings of this thesis are presented as well as the future directions of research in this area.