Exploring the role of viscosity-vaso-occlusion and haemolysis-endothelial dysfunction in pain sensitization among Jamaicans with sickle cell disease.

Viscosity-vaso-occlusion (VVO) and haemolysis-endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso-occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the adult sickle cell quality of life measurement information system. The 'elbow method' determined the optimal number of clusters as three. Clustering was performed using K-prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot-PPT, 6.8% higher hand-PPT and 2.5% higher hand-HPT and foot-HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist.

Numb chin syndrome in sickle cell disease: a case series of Jamaican patients.

Numb chin syndrome is an uncommon presentation that has been reported as secondary to metastatic disease, trauma, and infections of the maxilla, mandible, or oral cavity. The hypoesthesia, paraesthesia, or pain are a result of injury to the inferior alveolar nerve, which is particularly vulnerable as it exits the mandible through the mandibular foramen as the mental nerve. In persons with sickle cell disease, it has been reported as a manifestation of mandibular vaso-occlusive crisis. This case series presents 13 patients with sickle cell disease who presented with numb chin syndrome, the largest number of cases that has been described in the literature to date. The report illustrates the wide variety of presentations and therefore possible differential diagnoses to consider. In this case series, the symptoms were associated with vaso-occlusive crises, allergic reactions, dental infections, malignancy, rheumatoid arthritis, and pregnancy. Most appeared to be self-limiting; however, one patient was having his second episode, and the numbness has persisted in three patients. The series illustrates that it is important not only to ensure that the source of the local vaso-occlusive crisis is treated, but also to not miss important differentials such as metastatic disease, where this can be the first presentation of malignancy and would represent a very poor prognosis. There is no reported successful treatment for the hypoesthesia in this case series, and this presents an area for further research.

The clinical assessment of foreign body ingestions: Experience in a developing country.

Foreign body (FB) ingestion is an important emergency in low- to middle-income countries. Our study sought to identify which clinical and radiological findings best predict upper gastrointestinal FB impaction. Amongst 149 adolescents and adults presenting to two Jamaican hospitals between 2018 and 2020, FB's were found at 31% of telescopic laryngoscopies and 60% of rigid oesophagoscopies. Commonest sites of impaction were the tonsils at laryngoscopy (15/46) and proximal oesophagus at oesophagoscopy (17/22). Odds of pharyngeal impaction were higher with fish bone ingestion, persistent discomfort, perceived location of discomfort above the cricoid cartilage and symptoms noted during a meal. Persistent discomfort and FB shadow on X-ray imaging produced higher odds of oesophageal impaction. Simple clinical and radiological assessments are useful in predicting FB impaction in resource-limited settings.

Sickle Cell Disease and Pain: Is it all Vaso-occlusive Crises?

OBJECTIVES: Acute pain is the main complication of sickle cell disease. Chronic pain (CP) and neuropathic pain (NP) may also be experienced, but have not been formally described in Jamaican patients. A cross-sectional study was conducted to determine their prevalence and characteristics, and to determine the common pain locations and modalities of management. MATERIALS AND METHODS: All well individuals with sickle cell disease patients 14 years and older, not pregnant and without a history of clinical stroke were consecutively recruited. Anthropometric measurements, hematology studies, an analgesia checklist, and the Adult Sickle Cell Quality of Life Measurement Information System questionnaire were completed. The painDETECT questionnaire was completed to describe NP and pain patterns-from which CP was defined. RESULTS: There were 257 patients in total, with 55.6% being females; the mean age of the patients was 31.7±12 years, and 75% had the SS genotype. Almost all patients (92.6%) had had an acute pain crisis in their lifetime and 72.4% in the last year. The mean severity at last attack was 6.8±3.1 on a scale of 0 to 10. The prevalences of CP and NP were 21.5% and 17.9%, respectively. Female sex, the presence of current leg ulcers, and the use of a strong opioid in the last 4 weeks produced higher odds of NP, whereas older age, milder genotypes, and daily analgesic use had the highest odds of CP. Opioids were used by 40.1% of the patients in the previous 4 weeks, whereas nonpharmacological treatments such as physiotherapy was less used, but reported to be very effective. DISCUSSION: CP and NP should be assessed during routine care of sickle cell pain so that targeted therapies can be applied.

Health-related quality of life and neuropathic pain in sickle cell disease in Jamaica.

BACKGROUND: Health related quality of Life (HRQOL) is an important consideration when managing chronic diseases, like sickle cell disease (SCD). Assessment of neuropathic pain (NP) and its association with HRQOL in SCD are rarely reported. OBJECTIVES: To examine the prevalence of NP and its association with HRQOL in adult Jamaicans with SCD. METHODS: Adult SCD patients were recruited consecutively and data were collected on socio-demographics, NP using Douleur Neuropathique 4 (DN4), and HRQOL using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Means, medians, t-tests, ANOVA tests, Wilcoxon Rank-sum tests, Kruskal-Wallis tests, Pearson's correlation and multivariate linear regression analyses were performed using STATA 14.2. RESULTS: There were 236 respondents, with 56.8% female, mean age 33.2 years (SD: 11.6; range: 18-67 years), and 75% had homozygous SS genotype. NP was likely present in 26.7% of the population. The standardized ASCQ-Me (mean ± SD; ordered from lowest to best HRQOL domain scores) were: emotional impact 53.3 ± 10.1; sleep impact 56.1 ± 9.7; social function 57.7 ± 10.6; pain impact 58.6 ± 7.8; and stiffness impact 61.0 ± 7.3. On multivariate analyses, NP significantly reduced emotional and social functioning and worsened sleep and stiffness. Higher acute pain scores significantly worsened all HRQOL domains, while higher disease severity worsened all except stiffness. Obesity was associated with worse sleep and greater stiffness. Females with leg ulcers reported lower social functioning and unemployed females had greater pain impact. CONCLUSIONS: NP is increasingly prevalent in SCD and worsens HRQOL. Gender specific studies are needed to understand the significantly poorer HRQOL in women.

How Free Is Free Health Care? An Assessment of Universal Health Coverage Among Jamaicans with Sickle Cell Disease.

Purpose: In an effort to transition toward universal health coverage (UHC), Jamaica abolished user fees at all public health facilities in 2008. We aimed to determine the extent of out-of-pocket payments (OPPs) and the other cost barriers to UHC among patients with sickle cell disease (SCD). Methods: Patients presenting to the Sickle Cell Unit in Kingston, Jamaica, for routine care between October 2019 and August 2020 were consecutively recruited and interviewed about their latest hospitalization within the previous 4 weeks. Parents or guardians completed the questionnaire on behalf of pediatric patients. The questionnaire included the Patient Satisfaction Questionnaire Short Form (PSQ)-18 and the health module of the Jamaica Survey of Living Conditions. Results: There were 103 patients with ages ranging from 7 months to 56 years (51.5% female, 60.2% public hospitalizations, and 54.4% pediatric). The modal income (J$6200-$11,999 per week) was similar to the minimum wage and 48.5% lived in overcrowded households. Government drug-subsidy cards were owned by 39.8%. OPPs were made by 19.4% of persons for items and tests that were unavailable at public facilities. There were no costs reported by 69.6%, who visited public pharmacies. Similarly, the cost of admission to public hospitals was free for 95.4% of subjects. Using public transportation, private hospitalization, and having more disease complications were predictive of a perception that health care is unaffordable. Conclusion: Most SCD subjects reported no expense with public hospitalizations; however, approximately one in five reported OPPs. Efforts are needed to increase the availability of subsidized items, and the use of drug-subsidy cards, to improve UHC.

The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report.

BACKGROUND: It is important that multiple genetic diagnoses are not missed. This case report describes the clinical features and management of a patient with co-inheritance of Waardenburg syndrome type 4 or Waardenburg-Shah syndrome, an extremely rare disease, and homozygous sickle cell disease not uncommon in the Caribbean. This case is unusual as it may be the first documented case of the co-inheritance of both these diseases. Given the commonality of sickle cell and related hemoglobinopathies, such combined disorders are likely to be under-reported. Importantly, reporting this case will add to the medical literature as it will raise awareness of the phenotypic manifestations of this disorder. CASE PRESENTATION: A 54-year-old Afro-Caribbean woman had a delayed diagnosis of homozygous sickle cell disease at 7 years of age by hemoglobin electrophoresis. The complications of sickle cell disease she experienced included bone pain, a chronic right leg ulcer, avascular necrosis of her left hip, and symptomatic cholelithiasis. This diagnosis was preceded by an earlier diagnosis of Waardenburg syndrome. The basis for the diagnosis of Waardenburg-Shah syndrome was the presence of pigmentary disturbances of her eyes (hypoplastic blue irides), congenital sensorineural hearing loss, and Hirschsprung's disease. She was mute and complained of chronic constipation which required disimpaction on several occasions. She attended a school for the deaf and communicated via writing. A Duhamel procedure bypassing her rectum was performed at age 9. She died following an admission for acute chest syndrome complications. CONCLUSION: Sickle cell disease can be diagnosed by newborn screening but, as in this case, may have a delayed presentation. The delay in diagnosis of homozygous sickle cell disease illustrates that other genetic disorders should be considered in patients who already have a diagnosis of one Mendelian disorder but show atypical features.

Organization of afferents to the striatopallidal systems in the fire-bellied toad Bombina orientalis.

The cerebral hemispheres of amphibians display paired dorsal and ventral striatum (commonly referred to as striatum proper and nucleus accumbens, respectively). Each striatal region is proposed to be closely associated with a pallidal structure located caudal to it to form a striatopallidal system. In the present study, afferents to the dorsal and ventral striatopallidal systems of the fire-bellied toad (Bombina orientalis) were investigated using the neuronal tracer biocytin. A quantitative analysis of the topographical distribution of afferent neurons from the thalamus and posterior tubercle/ventral tegmentum was emphasised. The main results show that inputs to the two striatopallidal systems originate from distinct dorsal thalamic nuclei, with dorsal and ventral striatopallidal afferent neurons favouring strongly the lateral/central and anterior thalamic nuclei, respectively. However, afferent neuron distribution in the dorsal thalamus does not differ in the rostrocaudal axis of the brain. Afferent neurons from the posterior tubercle and ventral tegmentum, on the other hand, are organised topographically along the rostrocaudal axis. About 85 % of afferent neurons to the dorsal striatopallidal system are located rostrally in the posterior tubercle, while 75 % of afferent neurons to the ventral striatopallidal system are found more caudally in the ventral tegmentum. This difference is statistically significant and confirms the presence of distinct mesostriatal pathways in an amphibian. These findings demonstrate that an amphibian brain displays striatopallidal systems integrating parallel streams of sensory information potentially under the influence of distinct ascending mesostriatal pathways.

Modification of a prey catching response and the development of behavioral persistence in the fire-bellied toad (Bombina orientalis).

The present report investigated how fire-bellied toads (Bombina orientalis) modified their response in a prey catching task in which the attribution of food reward was contingent on snapping toward a visual stimulus of moving prey displayed on a computer screen. Two experiments investigated modification of the snapping response, with different intervals between the opportunity to snap at the visual stimulus and reward administration. The snapping response of unpaired controls was decreased compared with the conditioned toads when hour or day intervals were used, but intervals of 5 min produced only minimal change in snapping. The determinants of extinction of the response toward the visual stimulus were then investigated in 3 experiments. The results of the first experiment suggested that increased resistance to extinction depended mostly on the number of training trials, not on partial reinforcement or the magnitude of reinforcement during training. This was confirmed in a second experiment showing that overtraining resulted in resistance to extinction, and that the pairing of the reward with a response toward the stimulus was necessary for that effect, as opposed to pairing reward solely with the experimental context. The last experiment showed that the time elapsed between training trials also influenced extinction, but only in toads that received few training trials. Overall, the results suggest that toads learning about a prey stimulus progress from an early flexible phase, when an action can be modified by its consequences, to an acquired habit characterized by an increasingly inflexible and automatic response.