Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

OBJECTIVES: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. METHODS: A retrospective comparative analysis of HbSS, HbSC and HbSßThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. RESULTS: Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSßThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSßThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)). CONCLUSIONS: HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.

Antihypertensive medication class and diastolic orthostatic hypertension in older Caribbean adult patients.

In the Caribbean there is limited data on orthostatic hypertension (OHT) in elderly hypertensive patients with atherosclerotic disease who are at risk for cardiovascular events. The authors examined the association of antihypertensive classes of drugs with diastolic OHT in patients 60 year and older with hypertension and hyperlipidemia attending public primary care facilities. These relationships were evaluated in a cross-sectional study of hypertensive hyperlipidemic older patients (n = 400) to determine orthostatic changes in blood pressure based on seated to standing measurements. OHT was defined as an increase in systolic blood pressure of ≥20 mm Hg and/or increase in diastolic blood pressure of ≥10 mm Hg upon orthostasis at 3 min. Patients were categorized based on their orthostatic blood pressure response: orthostatic normotensive (n = 200) and blood pressure dysregulated (n = 200) of which 168 were diastolic OHT. Multivariable logistic regression models were used to examine associations of antihypertensive classes and diastolic OHT. Renin-angiotensin-aldosterone-system (RAAS) blockers were the most commonly prescribed (79.3%), followed by diuretics (DIUs) (61.6%), dihydropyridine calcium channel blockers (dCCBs) (53.8%), and beta-blockers (BBs) (19.3%). Most normotensive (76.0%) and diastolic OHT (75.0%) patients were prescribed two or more antihypertensive medications. Pharmaceutical prescription of triple combination RAAS blockers + dCCBs + DIUs (OR, 0.55; 95% CI, 0.31-0.99) or RAAS blockers + dCCBs + BBs (OR, 0.23; 95% CI, 0.06-0.92) showed a protective effect of diastolic OHT in analyses adjusted for age, sex, sitting diastolic blood pressure, and comorbidities. Our study suggests prescription of triple combination antihypertensive drugs of RAAS blockers + dCCBs + DIUs or RAAS blockers + dCCBs + BBs may reduce the likelihood of diastolic OHT.

Pregnancy outcomes in systemic lupus erythematosus: experience from a Caribbean center.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune multi-system disorder frequently affecting black women of childbearing age. No published data exist on the obstetric outcomes in a Caribbean population. OBJECTIVE: We analyzed pregnancy outcomes in an Afro-Caribbean cohort of women with SLE at a tertiary university hospital. METHODS: A retrospective cohort study was performed of all pregnant women with SLE prior to pregnancy from January 1990 to December 2021 at the University Hospital of the West Indies (UHWI), Jamaica. Maternal rheumatologic, obstetric, fetal/neonatal data were analyzed. Descriptive statistical analyses were performed. To determine if outcomes were associated with various factors, Spearman's rho was followed by logistic regression analysis to estimate unadjusted odds ratios with statistical significance at p < 0.05. RESULTS: A total of 56 pregnancies in 47 women were identified with SLE. Live births were 87.5%, with 10.7% spontaneous miscarriages and no neonatal deaths. Prednisone was the most used drug in 67.9% of patients. 85% of women had an adverse outcome with an adverse fetal outcome occurring in 55% of cases. Prednisone was associated with an adverse fetal/neonatal outcome (Spearman's rho = 0.38; p = .004). CONCLUSION: In this first Caribbean series on SLE in pregnancy, reasonably successful pregnancy outcomes are achievable in Afro-Caribbean women managed in multidisciplinary centers.

The Use of Biomarkers in Pharmacovigilance: A Systematic Review of the Literature.

Background: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs). Objective: The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area. Design: This is a systematic review of the literature. Data Sources and Methods: Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance. Results: Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories. Conclusion: Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.

Disparity between adolescents' health information needs and the information received in a middle-income country.

AIM: This study sought to identify adolescents' health information sources and determine the gap between what adolescents want to hear and what they actually hear from their healthcare providers (HCPs), a proxy for unmet health needs. METHODS: A cross-sectional study was conducted in four high schools conveniently selected in Jamaica to ensure adequate representation in rural and urban locales. Adolescents 11-19 years old with relevant assent/consent completed a paper-based self-administered questionnaire. Questions were adapted from the Young Adult Health Care Survey to determine proportion of adolescents receiving confidential care, the level of counselling offered and difference between location and unmet needs. RESULTS: Adolescents acknowledged multiple sources of information, with urban adolescents reporting television, radio and parents as sources more frequently than in rural setting (p < 0.05). They most commonly wanted to discuss weight management (n = 308, 64.2%), nutrition (n = 418, 87.1%), exercise (n = 361, 75.2%); and emotions they are experiencing (n = 246, 51.3%). Unmet needs differed by location; more rural than urban adolescents found that their desire to discuss school performance (p < 0.05) and sexual orientation (p < 0.05) was unmet, while more urban youth felt their need for discussions about STIs was unmet (p < 0.05), when compared to their rural counterparts. CONCLUSION: This study highlights that while there is some access to health information in Jamaica, especially via television, radio and internet, the needs of the adolescent population remain unmet. HCPs need to employ a patient-centred approach where confidentiality is established and screening is done for unmet needs in an effort to optimize health outcomes.

Awareness of inappropriate use related to antimicrobial resistance among medical doctors by country economic status: A systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is promoted by inappropriate use and is a greater burden for low to middle income countries (LMIC) than high income countries (HIC). OBJECTIVE: This systematic review aimed to compare the awareness of inappropriate use related to AMR among medical doctors from LMIC and HIC using published knowledge, attitude and practice (KAP) studies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, sequential systematic literature search of PubMed and Web of Science databases for articles published since inception up to June 1, 2022 for KAP studies involving medical doctors. Using fifteen KAP items related to promoting AMR, data on proportion of participants responding affirmatively was extracted and reported using means, ranges and 95% confidence intervals (CI). RESULTS: Forty-two studies met the inclusion criteria and involved 13,089 medical doctors from 11HIC and 21LMIC. All were cross-sectional studies, 71.4% involved non-probability sampling and 78.6% were of satisfactory quality. Knowledge items showed mean proportion of more medical doctors responding correctly. Similar affirmation trends were observed for attitude and prescribing practice items. Awareness appeared similar between medical doctors of the economic groups, except for a greater interest in training for LMIC (95.4%; 95%CI 93.0%, 97.9%) versus HIC (81.7%; 95%CI 65.6%, 97.9%). Countries with poor proportions were identified in both economic groups. CONCLUSION: For identified studies, trends suggest good awareness among medical doctors of the known inappropriate use and perceived threat of AMR, as well as prescribing practices to reduce the risk of AMR. Trends were similar across HIC and LMIC; however, countries with evidence of poor awareness exist in both economic groups.

Prevalence and distribution of ampc beta-lactamase producing escherichia coli and klebsiella pneumoniae isolates obtained from urine samples at a tertiary care hospital in the caribbean.

Introduction: The aim of this study was to investigate the prevalence and distribution of AmpC beta-lactamases (BLs) in uropathogens (E. coli and K. pneumoniae) at the University Hospital of the West Indies Jamaica (UHWI). Method: De-duplicated consecutive urine samples, collected from January to March 2020 at the UHWI, were analyzed. Screening and phenotypic confirmatory tests were conducted using resistance to cefoxitin and the Disc Approximation Test (DAT) respectively, for isolates of interest. Multiplex PCR was performed on cefoxitin resistant (CR) isolates for the detection of bla CIT, bla MOX, bla FOX, bla ACC, and bla DHA genes. Whole genome sequencing (WGS) was used to further detect AmpC BL genes in PCR negative isolates with indeterminate phenotypic results. Results: Sixty-four Gram negative isolates were obtained from 61 patients (55% female), aged 18 months to 88 years old. At least 35% (26) had complicated urinary tract infections. Only 7 out of 64 isolates were E. coli or K. pneumoniae, had antibiograms suggestive of possible AmpC BL production and were CR. DATs confirmed AmpC BL in two of these (1 K. pneumoniae; 1 E. coli), one tested negative (E. coli) and four had inconclusive results (K. pneumoniae). PCR detected bla DHA and bla CIT in two CR isolates. WGS further detected bla CMY-42 in one isolate. The prevalence of screened CR isolates with AmpC BL is 57.14% (4 of 7), representing 6.25% of the sample. AmpC BL producers tested had 100% susceptibility to meropenem and nitrofurantoin. Conclusion: AmpC BL prevalence among E. coli and K. pneumoniae, common urinary pathogens, in the studied isolates is low. Although cefoxitin screening is helpful, phenotypic screening using the DAT can yield indeterminate results best clarified by molecular testing.

Influence of Jamaican Cultural and Religious Beliefs on Adherence to Pharmacotherapy for Non-Communicable Diseases: A Pharmacovigilance Perspective.

Worldwide, socio-cultural determinants have been shown to influence the beliefs of patients about their health and decision making for treatment. This is consistent with the evidence that cultural and religious beliefs affect illness conceptualization and behaviors of Jamaican patients living with non-communicable diseases, such as diabetes mellitus and hypertension. Despite these known socio-cultural influences, an acknowledgment of relevance of adherence to pharmacotherapy has been grossly understudied. Furthermore, while poor adherence to pharmacotherapy, especially in the management of patients living with non-communicable diseases is associated with adverse drug reactions; reporting of such information in the pharmacovigilance process is inadequate. We review previous studies on the cultural and religious beliefs within the Jamaican context that may contribute to poor adherence to pharmacotherapy, especially among those patients living with non-communicable diseases. We support the ongoing perspective that current pharmacovigilance processes need retooling with the inclusion of socio-cultural influences on adherence to pharmacotherapy.

Lack of association between serum vitamin B12 and nocturnal sleep parameters following cyanocobalamin supplementation in healthy adults.

BACKGROUND: This study examined the effect of vitamin B12 supplementation on sleep parameters of latency, total sleep time, wake-after-sleep onset, total time in bed and sleep efficiency in healthy adults. METHODS: This quasi-experimental pre-test, post-test design recruited adults 25-50 years old, with normal vitamin B12 levels. Sleep parameters were assessed using Phillips Respironics Actiwatch-2® on non-dominant wrist from Monday to Thursday for four weeks. Pre-supplementation data was collected for the first two weeks; then participants started 3mg pre-packaged cyanocobalamin supplements daily for 14 days. Post-supplementation data was collected for weeks three and four. Serum was collected by venipuncture at the beginning and end of the study for vitamin B12 assay. Descriptive statistics involved median and interquartile range [IQR]. A comparison of the sleep parameters before and after cyanocobalamin supplementation was done using non-parametric inferential analysis. RESULTS: Fourteen healthy adult participants completed the study; nine females and five males with median age of 37[17] years and a normal range of serum vitamin B12 level (169-695 pmol/L). Median serum vitamin B12 level was significantly elevated following supplementation (355[217] to 961[679]) pmol/L; p = 0.020); but there was no change in any of the sleep parameters measured. Spearman's rho correlation analysis showed no correlation between serum vitamin B12 levels and the sleep parameters for pre-supplementation and post-supplementation weeks. CONCLUSION: Two weeks of cyanocobalamin supplementation (3mg/day) resulted in the expected increase in serum vitamin B12 levels in healthy adults but did not influence their sleep wake activity.

Trends in the utilization of nuclear medicine technology in Jamaica: Audit of a private facility.

This study sought to evaluate the types and frequencies of nuclear medicine studies that were carried out at a privately-run nuclear medicine facility in Kingston, Jamaica. Previous studies of this nature have not been done among this population, therefore the researchers sought to gather data which may prove to be useful for the growth of nuclear medicine practice in Jamaica. The study was a nonexperimental, retrospective study which involved an assessment of the records of all nuclear medicine patients who received a radiopharmaceutical during January 01, 2017, to December 31, 2018. The data extracted included age, gender, radiopharmaceutical administered, indication for study, and impression from scan. The total number of nuclear medicine scans that were carried out at the facility for the 2-year period was 3756. Of this number, 1889 (50.3%) were male and 1866 (49.7%) were female, with the age ranging from 3 months to 100 years. The types and frequencies of the most frequently occurring studies conducted were bone (2116, 56.3%), renal (867, 23.1%), thyroid (307, 8.2%), and lung (254, 6.8%). Patients aged 60 years and over accounted for the majority of the bone scans (1353/2116). The age group 26-59 years accounted for most of the scans of the lung (123/254), thyroid (209/307), parathyroid (34/65), and whole body (26/34). Patients under 12 years of age accounted for the majority of the renal (596/867), gastrointestinal (22/26), and hepatobiliary (16/28) scans. The audit of this private facility reflects the documented demand on the International Atomic Energy Agency database for Latin America and the Caribbean, and demonstrates the need for continuity of this specialized service in our population.

Enhancing Pharmacovigilance from the US Experience: Current Practices and Future Opportunities.

This review is intended to present perspectives from the US experience in enhancing pharmacovigilance on current practices and future opportunities. Best practices concepts could be applied worldwide through the presentation of how three pillars of pharmacovigilance: (1) medical and scientific excellence, (2) operational and compliance excellence, and (3) knowledge sharing and experts development in the field could serve as a framework for the establishment of an efficient and successful global pharmacovigilance system.

Dibenzyl trisulfide binds to and competitively inhibits the cytochrome P450 1A1 active site without impacting the expression of the aryl hydrocarbon receptor.

The toxicological manifestation of many pollutants relies upon their binding to the aryl hydrocarbon receptor (AHR), and it follows a cascade of reactions culminating in an elevated expression of cytochrome P450 (CYP) 1 enzymes. CYP1A1 and CYP1B1 are associated with enhanced carcinogenesis when chronically exposed to certain polyaromatic hydrocarbons, and their inhibition may lead to chemoprevention. We evaluated dibenzyl trisulfide (DTS), expressed in the ethnomedical plant, Petiveria alliacea, for such potential chemoprevention. Using recombinant human CYP1A1 and CYP1B1 bactosomes on a fluorogenic assay, we first demonstrated that DTS moderately inhibited both enzymes with half maximal inhibitory concentration (IC50) values of 1.3 ± 0.3 and 1.7 ± 0.3 µM, respectively. Against CYP1A1, DTS was a reversible, competitive inhibitor with an apparent inhibitory constant (Ki) of 4.55 ± 0.37 µM. In silico molecular modeling showed that DTS binds with an affinity of -39.8 kJ·mol-1, situated inside the binding pocket, approximately 4.3 Å away from the heme group, exhibiting interactions with phenylalanine residue 123 (Phe-123), Phe-224, and Phe-258. Lastly, zebrafish (Danio rerio) embryos were exposed to 0.08-0.8 µM DTS from 24 to 96 h post fertilization (hpf) with the in vivo ethoxyresorufin-O-deethylase (EROD) assay, and, at 96 hpf, DTS significantly suppressed EROD CYP1A activity in a dose-dependent manner, with up to 60% suppression in the highest 0.8 µM exposure group. DTS had no impact on gene transcription levels for cyp1a and aryl hydrocarbon receptor 2 (ahr2). In co-exposure experiments, DTS suppressed CYP1A activity induced by both B[a]P and PCB-126, although these reductions were not significant. Taken together, these results demonstrate that DTS is a direct, reversible, competitive inhibitor of the carcinogen-activating CYP1A enzyme, binding in the active site pocket close to the heme site, and shows potential in chemoprevention.

Evaluation of Plasma Circulating Cell Free DNA Concentration and Integrity in Patients with Prostate Cancer in Jamaica: A Preliminary Study.

BACKGROUND: Cell free circulating DNA (cfcDNA) is a promising diagnostic tool for prostate cancer (PCa). This study aimed to measure the cfcDNA concentration and integrity in PCa patients using quantitative polymerase chain reaction (qPCR) analysis. This study also assessed the correlation between these molecular biomarkers with total prostate-specific antigen (PSA), Gleason score, prostate volume, and age. METHODS: Eleven PCa patients and 9 persons with benign prostatic hyperplasia (BPH) were recruited. Blood samples were collected before prostate biopsy and plasma quantified by qPCR amplification of the ALU 115 DNA sequence, with the ratio of ALU 247 to ALU 115 reflecting cfcDNA integrity. RESULTS: There were no significant differences in median, interquartile range (IQR) cfcDNA concentration or cfcDNA integrity between the patients with PCa (47.9 (214.93) ng/mL; 0.61 (0.49)) and persons with BPH (41.5 (55.13) ng/mL, p = 0.382; 0.67 (0.45), p = 0.342). A weakly positive correlation exists between cfcDNA concentration and total PSA (r = 0.200, p = 0.555) but not with age or Gleason score in PCa patients. CONCLUSION: cfcDNA concentration was relatively nonsignificantly higher in PCa patients in comparison to persons with BPH, whereas cfcDNA integrity was similar in both groups. Though limited in sample size, this study shows that cfcDNA concentration may be a potentially valuable noninvasive biomarker for the diagnosis of PCa.

Introducing medical students to pharmacovigilance through a Basic Research Skills Special Study Module.

BACKGROUND: Pharmacovigilance is an important aspect of clinical practice; however, there is limited evidence that it exists as a theme in medical education curricula. OBJECTIVE: We developed and used a Basic Research Skill Special Study Module to introduce pharmacovigilance to medical students in the early years of their programme. METHODS: Students completing year one or two of the Faculty of Medical Sciences, Bachelor of Medicine, Bachelor of Surgery programme at The University of the West Indies, Jamaica participated in the four week experience from May 16th to June 12th 2019 to complete structured content sessions and self-directed activity. Sessions focused on the importance of pharmacovigilance and guided steps to complete a secondary data research project on an adverse reaction reported for a drug of personal interest. The final output was a poster mini-symposium at which each student held a five minute oral presentation. Posters were assessed for compliance with content guidelines, quality and presentation. RESULTS: Ten students participated in this experience and nine students produced posters of greater than 80% compliance with the content guidelines that were provided. The points awarded also reflected high scores for the required elements, relevant graphics, attractiveness/neatness and oral presentation. Students expressed overall satisfaction with the learning experience of the module. CONCLUSION: Moving forward, the authors will continue using this innovative active learning methodology to increase student exposure to pharmacovigilance, conducting and sharing research. Quantitative outcome assessment tools will be developed and long term goals will focus on its utility in curriculum improvement.

Sleep disorders and behavioral disorders in Jamaican children with epilepsy: A case-control study.

Children with epilepsy (CWE) are more likely to have sleep and behavioral disorders. With differences in reports, the aim was to evaluate sleep and behavior in Jamaican CWE and determine any association with epilepsy-related variables. Children with epilepsy were identified along with age and gender-matched controls from the University Hospital of the West Indies and the Bustamante Hospital for Children. Written informed consent was obtained followed by the completion of questionnaires assessing sleep, behavior, and background of both cases and controls. Parents of 61 children (26 cases and 35 controls) participated in the study. There was no difference in sleep scores or frequency of sleep disorders between cases and controls (p > 0.05). Children with epilepsy had worse scores than controls in peer problems (3.85 vs 2.32, p < 0.01), internal problems (7.42 vs 4.71, p < 0.01), and total behavioral problem (16.27 vs 12.09, p < 0.01). When compared with controls, CWE had a higher frequency of abnormal peer problems (66% vs 32%, p < 0.05) and emotional problems score (42% vs 15%, p < 0.05). Children with learning difficulty were three times more likely to have abnormal behavioral score Odds Ratio (OR) = 3.818, p < 0.05). Jamaican CWE have similar sleep scores to their healthy peers but have a higher frequency of peer and emotional problems.