Review/overview of pain in sickle cell disease.

Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids

Defining the phenotypes of sickle cell disease.

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among providers and researchers facilitates the implementation of appropriate and cost-effective diagnostic and therapeutic modalities. The aim of this review is to define the complications that are specific to sickle cell disease based on available evidence in the literature and the experience of hematologists in this field

Resource Utilization Due to Breakthrough Pain in Patients With Chronic Painful Conditions

Objectives Primary: To capture healthcare resource consumption and work loss in a population of patients with chronic pain who have pain flares from one or more non-cancer conditions. Secondary: To explore the relationship between anxiety, depression, and pain in this population

Amyand's hernia-a vermiform appendix presenting in an inguinal hernia: a case series

<p>Abstract</p> <p>Introduction</p> <p>A vermiform appendix in an inguinal hernia, inflamed or not, is known as Amyand's hernia. Here we present a case series of four men with Amyand's hernia.</p> <p>Case presentations</p> <p>We retrospectively studied 963 Caucasian patients with inguinal hernia who were admitted to our surgical department over a 12-year period. Four patients presented with Amyand's hernia (0.4%). A 32-year-old Caucasian man had an inflamed vermiform appendix in his hernial sac (acute appendicitis), presenting as an incarcerated right groin hernia, and underwent simultaneous appendectomy and Bassini suture hernia repair. Two patients, Caucasian men aged 36 and 43 years old, had normal appendices in their sacs, which clinically appeared as non-incarcerated right groin hernias. Both underwent a plug-mesh hernia repair without appendectomy. The fourth patient, a 25-year-old Caucasian man with a large but not inflamed appendix in his sac, had a plug-mesh hernia repair with appendectomy.</p> <p>Conclusion</p> <p>A hernia surgeon may encounter unexpected intraoperative findings, such as Amyand's hernia. It is important to be prepared and apply the appropriate treatment.</p

A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.

Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6% (133 samples) and control group subjects with HbF≤£3.1% (111 samples). Our GWAS results replicated SNPs previously identified in an erythroid-specific enhancer region located in the second intron of theBCL11Agene associated with HbF expression. In addition, we identified SNPs in theSPARC,GJC1,EFTUD2andJAZF1genes as novel candidates associated with HbF levels. To gain insights into mechanisms of globin gene regulation in theHBBlocus, linkage disequilibrium (LD) and haplotype analyses were conducted. We observed strong LD in the low HbF group in contrast to a loss of LD and greater number of haplotypes in the high HbF group. A search of knownHBBlocus regulatory elements identified SNPs 5\u27 of δ-globin located in an HbF silencing region. In particular, SNP rs4910736 created a binding site for a known transcription repressor GFi1 which is a candidate protein for further investigation. Another HbF-associated SNP, rs2855122 in the cAMP response element upstream of Gγ-globin, was analyzed for functional relevance. Studies performed with siRNA-mediated CREB binding protein (CBP) knockdown in primary erythroid cells demonstrated γ-globin activation and HbF induction, supporting a repressor role for CBP. This study identifies possible molecular determinants of HbF production

Perception of Breakthrough Pain in Patients with Chronic Painful Conditions

Objective: To understand how patients with chronic non-cancer pain define and describe pain flares

What determines auditory similarity? The effect of stimulus group and methodology.

Two experiments on the internal representation of auditory stimuli compared the pairwise and grouping methodologies as means of deriving similarity judgements. A total of 45 undergraduate students participated in each experiment, judging the similarity of short auditory stimuli, using one of the methodologies. The experiments support and extend Bonebright's (1996) findings, using a further 60 stimuli. Results from both methodologies highlight the importance of category information and acoustic features, such as root mean square (RMS) power and pitch, in similarity judgements. Results showed that the grouping task is a viable alternative to the pairwise task with N > 20 sounds whilst highlighting subtle differences, such as cluster tightness, between the different task results. The grouping task is more likely to yield category information as underlying similarity judgements

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification

Hydroxyurea and sickle cell anemia: effect on quality of life

BACKGROUND: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals. METHODS: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level (low or high) were investigated. RESULTS: Over two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5–9 (substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures. CONCLUSION: Treatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS