The Effect of PCSK9 Inhibitors on LDL-C Target Achievement in Patients with Homozygous Familial Hypercholesterolemia: A Retrospective Cohort Analysis.

INTRODUCTION: Achieving target low-density lipoprotein-cholesterol (LDL-C) levels remains challenging when treating homozygous familial hypercholesterolemia (HoFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are prescribed in addition to statins and ezetimibe, but patients' response varies and depends on residual low-density lipoprotein receptor (LDLR) function. METHODS: A multicenter, retrospective observational analysis evaluated LDL-C target achievement in response to PCSK9i treatment in 28 patients with HoFH from the Middle East/North Africa region. Effect of genotype was investigated. Demographic and clinical information was retrospectively obtained from medical records. Patient response to PCSK9i treatment was assessed by calculating percentage changes in lipid levels from pre-PCSK9i treatment baseline to most recent follow-up visit where patients were recorded as receiving PCSK9i on top of standard of care lipid-lowering therapies (LLTs; i.e., statins/ezetimibe) and assessing European Atherosclerosis Society (EAS) target achievement up to January 31, 2022. Lowest LDL-C level while receiving PCSK9i was identified. RESULTS: The cohort (n = 28) had a mean age (standard deviation; SD) of 22.8 (9.8) years (n = 28) and was 51% female (n = 27). Baseline LDL-C data were available in 24/28 (85.7%) patients (mean [SD] 14.0 [3.0] mmol/L). Median (interquartile range) duration of PCSK9i treatment was 12.0 months (4.0-19.1) months and mean (SD) % change in LDL-C after PCSK9i treatment was - 8.6% (12.1). LDL-C reduction from baseline was below 15% in 17/24 patients (70.8%). In the full cohort, mean (SD) minimum LDL-C during PCSK9i treatment was 11.9 (2.8; n = 28) mmol/L. No patient achieved EAS target LDL-C while receiving PCSK9i; genotype analysis suggested LDLR-null/null patients were most refractory to PCSK9i. CONCLUSION: Response to PCSK9i was minimal in this cohort of patients with HoFH. No patients achieved EAS LDL-C targets, and most failed to reach the EAS-recommended 15% LDL-C reduction for PCSK9i therapy continuation. These results suggest additional LLTs are necessary to achieve LDL-C targets in HoFH.

The impact of the implementation of computerized insulin order sets for the control of hyperglycemia in hospitalized cardiac patients.

Background: Glycemic control is crucial in managing hospitalized patients with type II diabetes (T2DM), and it presents as a clinical challenge in the cardiac population. Therefore, we aimed to evaluate the impact of computerized insulin order sets in T2DM hospitalized cardiac patients. Methods: A quasi-experimental, pre- and post-study design. We included T2DM patients who were hospitalized for at least 3 days. Patients undergoing cardiac surgery were excluded. The primary endpoint was the mean difference in random blood glucose level (BGL) before and after the implementation of insulin order sets. While the secondary endpoints were to compare the median differences in fasting BGLs and the number of hyperglycemic and hypoglycemic episodes during the first 7 days. The study consisted of three phases: pre-implementation, intervention and post-phase. In the intervention phase, insulin order sets were integrated into the electronic prescribing system, and education was provided to the cardiology department. The post-phase included the patient's post-implementations. Results: A total of 194 patients were enrolled during the study period. The mean random BGL was 11.17 mmol/L, 95% CI, 10.6-11.7 in the pre-phase and 9.5 mmol/L, 95% CI, 9-1 -9.9 mmol/L in the post-phase (P < 0.001). The median fasting BGL was 9.2 mmol/L (7.4-11.8, IQR) in the pre-phase and 8.5 mmol/L (6.6-10.3, IQR) in the post-phase (P = 0.027). The number of hypoglycemic episodes was 24 in pre-phase and 33 in post-phase (P = 0.13). Conclusion: The use of computerized insulin order sets was associated with potential improvements in random and fasting glycemic control without increasing the risk of hyperglycemia or hypoglycemia.

Establishment of reference interval for hemoglobin A1C and other hemoglobin subfractions for healthy Saudi adults.

BACKGROUND: The establishment of Reference Intervals (RIs) for Hemoglobin A1C and other hemoglobin subfractions (A1A, A1B, F, LA1C, A0) is of utmost importance in screening, diagnosing, and monitoring diabetes and other hemoglobin abnormalities through the application of high-pressure liquid chromatography (HPLC) technique. Because there are no locally established RIs for these parameters, it is essential to establish RIs specific to the Saudi population to accurately diagnose and monitor diabetic individuals and identify abnormal levels in hemoglobin subfractions. METHODS: As part of the IFCC global multicenter study of laboratory reference values, a cross-sectional study was conducted in Saudi Arabia. The study involved recruiting a total of 381 healthy adult subjects (>18 years, BMI 28.3 ± 6 kg/m2). Blood samples were analyzed for A1C, biochemical and other immunoassay parameters. The need for RIs based on sex, age, and BMI was determined using the standard deviation ratio (SDR) through a 3-level nested ANOVA. RESULTS: Based on the threshold of SDR≥0.4, RIs for A1C and other Hb subfractions were not partitioned by sex or BMI, but partitioned by age (<45 & ≥45 years) for A1C, LA1C, A0 and F. Spearman's correlation between glucose, insulin, and C-peptide showed a positive association with different hemoglobin subtractions of A1B, F, A1C, and LA1C. The RIs were obtained by using the parametric method and the latent abnormal values exclusion (LAVE) principle was applied on A1C. CONCLUSION: This study established RIs for A1C and other Hb subfractions for healthy adult Saudis. Age was found to be an important source of variation for most of the parameters including A1C. These findings will enhance the understanding and clinical decision-making concerning A1C and other hemoglobin subfractions. The elevated upper limit of RIs for A1C reflects the high prevalence of diabetes in the Saudi population specially in those with increased age.

Homozygous Familial Hypercholesterolemia (HoFH) in Saudi Arabia and Two Cases of Lomitapide Use in a Real-World Setting.

INTRODUCTION: Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition in which mutations in key peptides involved in the low-density lipoprotein receptor (LDL-R) pathway result in markedly elevated levels of circulating LDL-cholesterol (LDL-C). Patients are at high risk of developing early-onset atherosclerotic cardiovascular disease with associated mortality risks. Treatment options are extremely limited, and aspects of society and medical care in Saudi Arabia have the potential to increase incidence and limit treatment pathways in HoFH. METHODS: Along with a brief review of the evidence available on HoFH we describe the treatment of two Saudi Arabian patients with HoFH diagnosed and treated in accordance with local clinical practices and with the microsomal triglyceride transferase protein inhibitor lomitapide. RESULTS: HoFH in Saudi Arabia is characterized by problems associated with consanguinity, a lack of access to lipoprotein apheresis, and pressures to proceed to liver transplant. Among the case histories, the first patient was commenced on lomitapide therapy, and underwent a dramatic decrease in LDL-C levels from 16.5 to 2.2 mmol/L (87% decrease). This patient had problems with access to lomitapide and cessation of the drug resulted in rebound in LDL-C to 22 mmol/L. The second patient experienced delayed commencement of lomitapide therapy. Despite a 45% decrease in LDL-C levels from 15.3 to 6.9 mmol/L, the patient died the following year at age 26 years from complications subsequent to cardiovascular surgery. Lomitapide was well tolerated in both patients DISCUSSION: The experience of these two cases highlights the need for prompt, effective, and sustained intervention in HoFH to prevent cardiovascular morbidity and mortality. Lomitapide is an effective therapy for HoFH, and we look forward to improved access to this drug in Saudi Arabia, where there is a chronic unmet medical need in HoFH.

Managing Type 1 Diabetes among Saudi adults on insulin pump therapy during the COVID-19 lockdown.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has affected people's lives including patients with type 1 diabetes mellitus (T1DM). We aimed to investigate the impact of the COVID-19 lockdown on psychological status, self-management behaviors, and diabetes care maintenance among Saudi adults with T1DM using insulin pump therapy. METHODS: This cross-sectional study used a web survey to collect data on Saudi adults with T1DM who were treated in the specialized insulin pump clinic at King Abdulaziz Medical City-Jeddah, Saudi Arabia. We used the Patient Health Questionnaire-9 and General Anxiety Disorder-7 scales to measure depression and anxiety. RESULTS: Of the 70 patients who received the survey, 65 completed it. Overall, 23.1% and 29.2% of the patients reported moderate to severe and mild depression, respectively; 18.5% and 24.6% reported moderate to severe and mild anxiety, respectively. Compared with pre-lockdown, adherence to a healthy diet and regular physical activity decreased in 67.7% and 41.5% of the patients, respectively. Most patients maintained their adherence to insulin pump behaviors; frequent self-monitoring of blood glucose increased in 47% of glucometer users. Most patients benefited from phone visits or virtual education sessions, but 66.2% of the patients reported difficulty obtaining at least one type of insulin pump supply. CONCLUSIONS: Promoting self-management behaviors and psychological wellbeing of patients with T1DM using insulin pump therapy is crucial during a lockdown. Telemedicine is a useful alternative to in-person appointments, but strategies to ensure that patients have access to adequate resources during lockdown must be developed.

Perception of virtual clinics among Saudi adults with type 1 diabetes during the COVID-19 pandemic.

BACKGROUND AND AIMS: We aimed to assess patient perception toward the rapid implementation of virtual phone clinics among Saudi adult patients with type 1 diabetes mellitus (T1DM) during the coronavirus disease (COVID-19) pandemic. METHODS: This cross-sectional, web-based study included Saudi adult patients with T1DM who attended at least one virtual phone visit with the diabetes clinic at King Abdulaziz Medical City, Jeddah, Saudi Arabia, between August 1 and December 31, 2020. Patients anonymously answered a Google form-created Arabic questionnaire. Information about patient characteristics, outcome, and perception of the virtual phone visit were obtained. Data were presented using descriptive statistics, chi-square, one-way ANOVA, independent t-, and Welch's t-tests. RESULTS: The questionnaire was sent to 281 patients, of whom 201 completed it. 59.2% patients were satisfied with their overall virtual phone clinic experience, and 75.6% preferred to continue attending the virtual phone clinics in the future. The average perception value of patients toward virtual phone clinics was 67.76 ± 19.9, suggesting good perception among the majority. Negative or neutral views of current health, asking to be physically seen, and missing a virtual appointment were associated with significantly lower average patient perception value (p < 0.001). CONCLUSIONS: Most Saudi patients with T1DM have adapted to virtual phone consultations, exhibiting good satisfaction and perception, and high preference to continue using this system in the future. The utilization of the service to assist patients with diabetes is highly encouraged, especially during the COVID-19 pandemic. Strategies need to be developed to further enhance the patient experience.

Comparison Between the Treatment Modalities for Graves' Disease at King Abdulaziz Medical City, Jeddah.

Background Graves' disease is the most common cause of thyrotoxicosis. It can be treated using three different modalities, which include anti-thyroid drugs (ATD), radioactive iodine (RAI), and near-total thyroidectomy. This cohort study aimed to assess the treatment modality preferred at King Abdulaziz Medical City (KAMC) and to compare the treatment options in relation to the prognosis of the disease. Methods A retrospective cohort study was conducted on a total of 100 patients with Graves' disease who were treated and followed up in the endocrine clinics at KAMC between January 2013 and December 2018. Data on age at diagnosis, duration of illness, treatment modality, and response to treatment were extracted from paper and electronic medical files and analyzed. Results A total of 100 patients with Graves' disease were included in this cohort study. The ratio of female:male was 2:1. The median age in years was 32 (16). They were treated with ATD (60%), RAI ablation (40%), and none were treated by surgery. The remission rate was 53.3% for patients treated with ATD and 95% for RAI ablation. Hypothyroidism occurred in 90% of the responders to RAI and in 12% that were treated with ATD. Most of the patients that relapsed underwent RAI as the second line of treatment. Their remission rate was 78.6%. Conclusion ATD was the treatment modality mostly used for Graves' disease in our center. It resulted in a remission rate of 53%, which is higher than reported in national studies. Although the rate of remission post RAI ablation was as high as 95%, most patients developed hypothyroidism.

Hypoglycemic Risk Factors Among Hospitalized Patients with Type 2 Diabetes Mellitus at King Abdulaziz Medical City, Jeddah.

Background Hypoglycemia is a pathological condition in which the serum glucose level measures less than 3.0 mmol/L. It is a well-known complication in patients with diabetes mellitus. Age, body weight, gender, insulin usage, nutritional therapy, body mass index (BMI), the presence of diabetes complications, intensive care unit admission, and infection were reported as possible risk factors that may increase the risk of hypoglycemia. Therefore, this study aimed to analyze predisposing factors for hypoglycemia among hospitalized patients with type 2 diabetes in King Abdulaziz Medical City. Method This is a retrospective, case-control study design. The study included 326 hospitalized patients with type 2 diabetes; 152 experienced hypoglycemia (blood glucose <3.9) at least once during hospitalization and have been compared to 174 in the non-hypoglycemic group (blood glucose ≥3.9). Data were extracted from their electronic medical records (EMRs). Results This study reported that patients with lower BMI (28.80 ± 7 versus 31.20 ± 12.93) experienced hypoglycemia (P-value 0.044). Those hospitalized with infections or had acquired infections or required intensive care unit (ICU) admission during hospitalization had a higher risk to develop hypoglycemia (P-value 0.005, 0.003, and <0.001, respectively). Moreover, the use of multiple doses of insulin therapy or basal-plus insulin therapy was associated with a higher risk of hypoglycemia (P-value 0.012 and 0.028, respectively). Those on supplemental insulin were less likely to develop hypoglycemia (P-value <0.001). Patients on oral feeding had a lower chance of having a hypoglycemic attack (P-value 0.002) while those on tube feeding had double the odds (OR=2.37). Conclusions Infection, intensive care unit admission, lower body mass index, insulin regimen and nutritional therapy (enteral feeding and nothing-per-mouth (NPO)) were correlated with an elevated risk of having hypoglycemia in hospitalized patients with type 2 diabetes mellitus.

Serum insulin-like growth factor binding protein-1: an improvement over other simple indices of insulin sensitivity in the assessment of subjects with normal glucose tolerance.

BACKGROUND: Insulin resistance is associated with an increased risk of cardiovascular disease and diabetes. It can be assessed using complex reference techniques, such as clamp or frequently sampled intravenous glucose tolerance test (FSIVGTT). Therefore, simple indices derived from fasting insulin and glucose concentrations have been proposed. The aim of this study is to assess fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) as a simple index of insulin sensitivity compared with other simple indices and FSIVGTT. METHODS: Fasting serum IGFBP-1, fasting plasma insulin (FPI), homeostasis model assessment (HOMA-IR), quantitative insulin check index (QUICKI), fasting glucose to insulin ratio (FGIR), Raynaud and insulin glycaemic index (ISI-gly) were correlated with FSIVGTT (Si) in 22 subjects with normal glucose tolerance (NGT) and nine with impaired fasting glucose (IFG). RESULTS: In NGT individuals, IGFBP-1 correlated more strongly with Si than did any other index both before (r = 0.76) and after (r = 0.79) natural logarithm (ln) transformation. In subjects with IFG, IGFBP-1 was weakly correlated with Si before and after ln-transformation (r = 0.55, r = 0.56, respectively), but ISI-gly was the index most strongly correlated with Si (r = 0.77, r = 0.85, respectively). CONCLUSIONS: In subjects with NGT, fasting serum IGFBP-1 could be used as a simple reliable marker of insulin sensitivity. For more accurate estimation of insulin sensitivity in normal subjects and those with IFG, ln-transformation is preferred over raw data.

Thyroid Nodules Cytopathology Applying the Bethesda System with Histopathological Correlation.

BACKGROUND: Fine-needle aspiration cytology remains a valuable screening tool for preoperative management of thyroid nodules. However, the rates of false-negative and false-positive diagnosis remain a challenge for pathologists. OBJECTIVES: To assess the value of thyroid fine-needle aspiration as a screening tool and its accuracy of diagnoses relative to final histological diagnoses. PATIENTS AND METHODS: A chart review was conducted of all adult patients who underwent fine-needle aspiration of thyroid nodule(s) and were subjected to thyroid surgery at King Abdulaziz Medical City, Jeddah, Saudi Arabia, between January 2007 and June 2014. The fine-needle aspiration results were correlated with final histopathology results. RESULTS: Of the 408 aspirates from 373 patients, the Bethesda System for Reporting Thyroid Cytology (BSRTC) diagnostic categories were as follows: nondiagnostic in 26 aspirates (6.4%); benign in 128 (31.4%); atypia/follicular lesion of undetermined significance in 52 (12.7%); follicular neoplasm/suspicion for a follicular neoplasm in 83 (20.3%); suspicious for malignancy in 23 (5.6%) and malignant in 96 (23.5%). The comparative histopathological diagnoses were benign in 192 (47.1%) and malignant in 216 (52.9%) aspirates. The calculated risk of malignancy in the fine-needle aspiration categories was 34.6% in diagnostic category (DC) I, 15.6% in DC II, 50% in DC III, 52% in DC IV, 95.7% in DC V and 100% in DC VI. The sensitivity of fine-needle aspiration with BSRTC was 88.9%, specificity was 75.6%, positive predictive value was 79.7%, negative predictive value was 84.4% and accuracy was 81.5%. CONCLUSION: The results of this retrospective study demonstrated higher risks of malignancy in DC I, DC II, DC III and DC IV than that of the original BSRTC definition, along with a higher specificity and positive predictive value for cancer diagnosis, and a lower sensitivity and negative predictive value.

Biological variation in fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) among individuals with a varying glucose tolerance.

OBJECTIVE: To evaluate the biological variation of serum insulin-like growth factor binding protein-1 (IGFBP-1) in individuals with different degrees of glucose tolerance. RESEARCH DESIGN AND METHODS: IGFBP-1 was measured in 42 fasted subjects with: normal glucose tolerance (NGT=15), impaired fasting glucose (IFG=9), impaired glucose tolerance (IGT=9) and type 2 diabetics (DM=9). Short- and long-term reproducibility was determined for IGFBP-1. RESULTS: The longer-term reproducibility (CV) of serum IGFBP-1 was 20.9%, 29.5%, 33.1% and 48.0% for subjects with NGT, IFG, IGT and DM respectively. The results for the short-term serum IGFBP-1 yielded CVs for these same respective categories of 8.2%, 16.1%, 29.2% and 13.8%. CONCLUSIONS: IGFBP-1 measurement was least variable in NGT individuals over both long-term and short-term intervals and variability increased with deteriorating glucose tolerance. Due to its biological variation, IGFBP-1 serum level is more reliable in normal subjects than in individuals with type 2 diabetes.