Prospective cohort study of vitamin D deficiency in pregnancy: Prevalence and limited effectiveness of 1000 IU vitamin D supplementation.

BACKGROUND: Vitamin D deficiency is highly prevalent worldwide among pregnant women. Although vitamin D supplementation is effective in improving vitamin D status, the safety and optimal dosing of vitamin D supplementation during pregnancy remain less well understood. OBJECTIVE: This study aimed to investigate the prevalence of vitamin D deficiency among pregnant women and evaluate the effectiveness of vitamin D supplementation in improving vitamin D status during pregnancy. DESIGN: This prospective cohort study assessed the impact of a 16-week daily vitamin D supplementation 1000 IU regimen on vitamin D status among pregnant women. METHODS: A total of 365 pregnant women were recruited, and their baseline total circulating 25-hydroxy vitamin D concentrations were measured. Of these, 249 participants completed the study, which involved oral daily supplementation with 1000 IU of vitamin D and a repeat of total circulating 25-hydroxy vitamin D concentrations after 16 weeks. RESULTS: The study found that 57.7% of the participants had vitamin D deficiency, consistent with the rates reported in other studies. However, vitamin D supplementation at a dose of 1000 IU had a small effect size and was not clinically significant. However, 67% of participants with vitamin D deficiency remained deficient; among participants initially with vitamin D insufficiency, 30% became deficient. Moreover, 26.5% of individuals with sufficient vitamin D status at 12 weeks showed insufficient levels by 28 weeks. CONCLUSION: Vitamin D deficiency is widespread among pregnant women, and vitamin D supplementation at a daily dose of 1000 IU may not adequately address this problem. Although the study has limitations, its results align with previous research and may apply to other populations with a high prevalence of vitamin D deficiency during pregnancy. Further research is necessary to determine the most effective approach for addressing prenatal vitamin D deficiency.

Prevalence and effectiveness of vitamin D supplementation during pregnancyVitamin D deficiency is common among pregnant women and can lead to various health issues. This study aimed to investigate the effectiveness of vitamin D supplementation in improving vitamin D levels during pregnancy. A total of 365 pregnant women were recruited, and their vitamin D levels were measured at the beginning of the study. The participants were given a daily vitamin D supplement of 1000 IU, and their vitamin D levels were measured at 3-month intervals. The study found that more than half of the participants had vitamin D deficiency, which is consistent with the rates reported in other studies. However, vitamin D supplementation at the given dosage had a small effect and did not significantly increase vitamin D levels in pregnant women. Moreover, vitamin D-rich diets had no significant impact on vitamin D levels. The study emphasizes the importance of identifying effective strategies for preventing and treating vitamin D deficiency during pregnancy. The findings suggest that current strategies advised by international and national guidelines may not be sufficient to address the problem. Further research is needed to identify more effective approaches, including screening, higher safe dosages, and monitoring responses after 3 months of treatment. In summary, vitamin D deficiency is common among pregnant women, and current strategies may not be enough to address the issue. The study highlights the need for effective approaches to prevent and treat vitamin D deficiency during pregnancy, and further research is needed to find these strategies.

Advancing Artificial Intelligence for Clinical Knowledge Retrieval: A Case Study Using ChatGPT-4 and Link Retrieval Plug-In to Analyze Diabetic Ketoacidosis Guidelines.

Introduction This case study aimed to enhance the traceability and retrieval accuracy of ChatGPT-4 in medical text by employing a step-by-step systematic approach. The focus was on retrieving clinical answers from three international guidelines on diabetic ketoacidosis (DKA). Methods A systematic methodology was developed to guide the retrieval process. One question was asked per guideline to ensure accuracy and maintain referencing. ChatGPT-4 was utilized to retrieve answers, and the 'Link Reader' plug-in was integrated to facilitate direct access to webpages containing the guidelines. Subsequently, ChatGPT-4 was employed to compile answers while providing citations to the sources. This process was iterated 30 times per question to ensure consistency. In this report, we present our observations regarding the retrieval accuracy, consistency of responses, and the challenges encountered during the process. Results Integrating ChatGPT-4 with the 'Link Reader' plug-in demonstrated notable traceability and retrieval accuracy benefits. The AI model successfully provided relevant and accurate clinical answers based on the analyzed guidelines. Despite occasional challenges with webpage access and minor memory drift, the overall performance of the integrated system was promising. The compilation of the answers was also impressive and held significant promise for further trials. Conclusion The findings of this case study contribute to the utilization of AI text-generation models as valuable tools for medical professionals and researchers. The systematic approach employed in this case study and the integration of the 'Link Reader' plug-in offer a framework for automating medical text synthesis, asking one question at a time before compilation from different sources, which has led to improving AI models' traceability and retrieval accuracy. Further advancements and refinement of AI models and integration with other software utilities hold promise for enhancing the utility and applicability of AI-generated recommendations in medicine and scientific academia. These advancements have the potential to drive significant improvements in everyday medical practice.

Exploring ChatGPT's Potential in Facilitating Adaptation of Clinical Guidelines: A Case Study of Diabetic Ketoacidosis Guidelines.

Background This study aimed to evaluate the efficacy of ChatGPT, an advanced natural language processing model, in adapting and synthesizing clinical guidelines for diabetic ketoacidosis (DKA) by comparing and contrasting different guideline sources. Methodology We employed a comprehensive comparison approach and examined three reputable guideline sources: Diabetes Canada Clinical Practice Guidelines Expert Committee (2018), Emergency Management of Hyperglycaemia in Primary Care, and Joint British Diabetes Societies (JBDS) 02 The Management of Diabetic Ketoacidosis in Adults. Data extraction focused on diagnostic criteria, risk factors, signs and symptoms, investigations, and treatment recommendations. We compared the synthesized guidelines generated by ChatGPT and identified any misreporting or non-reporting errors. Results ChatGPT was capable of generating a comprehensive table comparing the guidelines. However, multiple recurrent errors, including misreporting and non-reporting errors, were identified, rendering the results unreliable. Additionally, inconsistencies were observed in the repeated reporting of data. The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention. Conclusions Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation. Future research should focus on improving the accuracy and reliability of ChatGPT, as well as exploring its potential applications in other areas of clinical practice and guideline development.

Breast Cancer Knowledge, Attitudes and Practices amongst Women in Qatar.

This cross-sectional study examines knowledge, attitudes, and practices surrounding breast cancer awareness and screening among women residents in Qatar. Females, >18 years old, registered with the Primary Health Care Corporation were invited to complete an Arabic or English online survey using a modified version of the Breast Cancer Awareness Module. Of the 9008 participants, 69% report awareness of breast cancer warning signs, but the results did not substantiate these claims. There remains a disconnect between participants' perceived awareness of their ability to detect breast cancer and their actual recognition of individual signs and symptoms. Nearly half (45.4%) report rarely or never checking their breasts for abnormalities (44.6%). Breast self-examination (BSE) and Breast Cancer Screening (BCS) uptake is low and many are unaware of the starting age for invitation to Qatar's BCS program. While only 18% of women report receiving an invitation, 94% attended, indicating that the BCS invitation is a remarkably effective means of improving screening uptake. Policymakers should capitalize on early recognition, which is possible in the youthful population. Broadening awareness campaigns and interventions targeting a broader audience including males, community and religious leaders and healthcare professionals may prove more effective in Arab communities.

Diagnostic accuracy of the Patient Health Questionnaire 2 (PHQ-2) in Qatar's primary care settings.

This cross-sectional study was designed to establish diagnostic accuracy of the Patient Health Questionnaire 2 in Qatar's primary care population. The data required for the study were anonymously extracted from Qatar's primary care electronic medical record system. The sensitivity, specificity, predictive values, negative values and optimal cut-off points were calculated for the tool. A total of 6921 individuals met the study's inclusion criteria. The diagnostic accuracy of cut-off values was calculated for scores 1-6. Based on the Youden's index (0.58), a score of 2 was identified as the most optimal cut-off. It offers a sensitivity of 88.73% and specificity of 69.31%. Further studies should aim to confirm the results using alternative study designs and to report them in accordance to population characteristics both in Qatar and internationally.

Haemoglobin cut-off values for the diagnosis of anaemia in preschool-age children.

BACKGROUND: The World Health Organisation (WHO) suggests haemoglobin that (Hgb) cut-off levels below 2SD from the population mean to initiate anaemia investigations. In the absence of epidemiological data, Hgb less than 11 g/dL is considered abnormal in children up to the age of 59 months (4 years and eleven months). OBJECTIVES: This study reports on the Hgb cut-off levels among children at 1 and 4 years of age. The study compared the prevalence based on the WHO generic cut-off levels and population-specific cut-off-based value defined as below 2SD from the population mean. DESIGN, SETTINGS, AND PARTICIPANTS: A cross-sectional record-based study of healthy children below the age of 59 months attending primary care settings in Qatar. 3 years of Hgb data were collected and analysed using descriptive analyses. We excluded children with any pre-existing disease or who have altered biological parameters indicating a non-healthy child. RESULTS: 39407 Participants were stratified into different sub-groups according to age, gender, and ethnicity. Hgb levels were expressed as the mean ± 2SD for children of one and four years of age. Most children were from Western Asia (45.6%), followed by Northern Africa (23.7%), and Southern Asia (21.7%). Our findings for one-year-old children cut-off levels for anaemia might be as low as 9.9 g/dL and 10.6 g/dL for 4-years old. CONCLUSION: Hgb cut-off values may be set at higher levels for one-year and four-year age groups and many different ethnicities. Higher cut-off points may overestimate the problem as a public health issue. Children may be unnecessarily treated with iron or have needless investigations.

Estimating point prevalence of COVID-19 in Qatar's primary care registered population: an RT-PCR drive-through study protocol.

BACKGROUND: The first COVID-19 cases in Qatar were reported on 29 February 2020. As the epidemic progresses, essential epidemiological information is needed to facilitate monitoring of COVID-19 in the population and plan the pandemic response in Qatar. AIM: The primary aim of this cross-sectional study is to estimate the point prevalence of COVID-19 in Qatar's primary care registered population. DESIGN & SETTING: A cross-sectional study design will be utilised. One publicly funded health centre from each of three geographical regions in Qatar will be identified as a study location and set up to facilitate a drive-through for the study. METHOD: Primary Health Care Corporation (PHCC) is publicly funded and the largest primary care provider in Qatar. The study will include randomly selected individuals from the full list of PHCC's registered population on its electronic medical records system. The sample selection will be done using a proportional to size sampling technique stratified by age, sex, and nationality representative of the overall PHCC-registered population. Considering the total population registered in PHCC, a sample of 2080 is proposed. A questionnaire will be administered to collect sociodemographic information, and nasal and throat swab samples will be taken. Data will be analysed to report overall symptomatic and asymptomatic point prevalence of COVID-19. CONCLUSION: This study, with the help of a randomly selected representative sample from Qatar's primary care registered population, will provide results that can be applied to the entire population. This study design will closely represent a real-world scenario of the outbreak and is likely to provide important data to guide COVID-19 pandemic planning and response in Qatar.

Haematological abnormalities and risk of COVID-19 infection in adult patients attending primary healthcare settings.

Centres for Disease Control and prevention (CDC) reports that there are limited data and information about the impact of underlying medical conditions and the risk of infection. To date, there are no studies that report on the risk of infection among patients with haematological diseases or abnormalities. This cross-sectional study reports on the baseline complete blood count in patients attending publicly funded primary care settings with a diagnosis of suspected COVID-19 infections in the state of Qatar. The study will report on the descriptive characteristics of the population, including gender, age and prior abnormalities to their blood test results. We will compare the results of those with positive and negative PCR test results, where appropriate. Nine hundred sixty-two adult patients attended publicly funded primary health care settings in the state of Qatar between February the 10th and April the 30th 2020 with a diagnosis of suspected COVID-19 infections had prior recorded blood investigations in the last six months and were included in this study. The population was young, mean of age is 38.8±11.6. (Median: 36 [Min: 19 - Max: 85]). Complete blood count of the sample had minimal missing data points. Females were more presented in our samples, Female (n=560, 58.21%) and Male (n=402, 41.79%). Most of our sample had a documented PCR test result, negative (n=831, 86.38%); positive (n=123, 12.79%) and missing (n=8, 0.83%). Low haemoglobin values (n=265, 27.5%) and low red blood cell count (n =170, 17.7%) were the most prevalent complete blood count abnormality in the population. Leukopenia was less common (n=50, 8.2%). Most of the population had normal platelet count (n=895, 93%). Gender was the most influential factor in our sample to increase the odds of having a positive PCR test results; males were more likely to be affected (P<0.001, Chi-square test) (OR 2.56, 95% CI 1.73-3.77). Categories for haematological abnormalities were not associated with increased risk of having a positive PCT test result. In a population attending primary healthcare settings with early presentation of symptoms of COVID-19 infection, the risk of infection among our cohort was not affected by the prior haematological values of those patients. Gender was the most influential parameter in the risk of infection in our population. Analysis of the results using gender-specific categories for different haematological parameters suggested that patients with abnormal haematological values were not at increased risk of having a positive COVID-19 infection.

Significance of Serum Adiponectin and Insulin Resistance Levels in Diagnosis of Egyptian Patients with Chronic Liver Disease and HCC.

One possible hypothesis for pathogenesis of hepatocellular carcinoma is deregulated expressed adipokines (adipose tissue cytokines). Chronic inflammation in the cirrhotic liver adipose tissue is associated with a modification in adipokine secretion. Changes in serum levels of adiponectin are known to be associated with the development of insulin resistance. Increased insulin resistance is a pathophysiological feature of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease. In addition, it was suggested that liver cancer development is probably connected with insulin resistance. The aim of this study is to evaluate the significance of serum Adiponectin level and insulin resistance in patients with chronic liver disease and hepatocellular carcinoma. Patient and Methods: 100 patients were enrolled in this cross sectional study and divided as following: Group I: 52 HCV patients with chronic liver disease (CLD).Group II: 48 patients with hepatocellular carcinoma (HCC). For all subjects, Serum Adiponectin and Insulin Resistance parameters (Fasting serum Insulin, Fasting serum Glucose, HOMA IR) were measured. Results: Serum Adiponectin was significantly lower in patients with hepatocellular carcinoma (p=0.000 ) and it is inversely correlated to tumor size and the number (p= 0.0001).Meanwhile, Insulin Resistance parameters (Fasting s. Insulin, Fasting s. Glucose, HOMA IR) were significantly higher in HCC patients than CLD patients (p= 0.0001). Conclusion: Insulin Resistance is significantly associated with the development of HCC. Serum level of Adiponectin may guard against HCC development among patients with chronic liver disease.

Caffeine Toxicity Following Ingestion of an Exercise Supplement by a Patient with Type 1 Diabetes.

We report the case of a patient with type 1 diabetes who developed acute severe diabetic ketoacidosis following ingestion of an energy supplement containing caffeine. Some 95% of the US adult population consume caffeine, and the general perception is that there are no negative consequences for health. The upper limit of safe consumption is less than 400 mg per day. However, acute ingestion of high doses of caffeine may cause significant metabolic changes that can be fatal. Here the patient consumed a toxic dose of caffeine causing unpleasant and puzzling symptoms, vomiting and, following omission of his long-acting basal insulin, severe diabetic ketoacidosis. As the sports nutrition market continues to expand, providers and manufacturers have a responsibility to give clear and accurate dosing instructions as well as side effect profiles for their products, particularly for diabetic patients. LEARNING POINTS: The impact of caffeine on blood glucose levels has implications for people with diabetes who may be thinking of consuming supplements containing caffeine.Providers of sports supplements have a responsibility to provide an accurate description of the side effects with a clear warning for diabetic patientsLegislators should review protocols for regulating the sports and nutritional supplements industry.

An exact model for predicting tablet and blend content uniformity based on the theory of fluctuations in mixtures.

Content uniformity (CU) of tablets is a critical property that needs to be well controlled in pharmaceutical products. Methods that predict the CU accurately can greatly help in reducing the development efforts. This article presents a statistical mechanical framework for predicting CU based on first principles at the molecular level. The tablet is modeled as an open system that can be treated as a grand canonical ensemble to calculate fluctuations in the number of granules and thus the CU. Exact analytical solutions to hard sphere mixture systems are applied to derive an expression for the CU and elucidate the different factors that impact CU. The model was tested against literature data and a large set of tablet formulations specifically made and analyzed for CU using a model active pharmaceutical ingredient. The formulations covered the effect of granule size, percentage loading, and tablet weight on the CU. The model is able to predict the mean experimental coefficient of variation (CV) with good success and captures all the elements that impact the CU. The predictions of the model serve as a theoretical lower limit for the mean CV (for infinite batches or tablets) that can be expected during manufacturing assuming the best processing conditions.

Development of tamper deterrent formulations: state of the pharmaceutical industry.

Prescription drug abuse is a significant and growing health and socio-economical problem in the US and the world. According to the 2008 UN World Drug Report, the number of people who have consumed an illicit drug at least once in 2006/2007 reached 240 million, roughly 6% of the world population aged 15 to 64. In the last few years, pharmaceutical manufacturers started developing new formulations specifically designed to provide tamper deterrent features. The initial focus of these development activities was extended release opioids, owing to their dominant share of reported prescription drug abuse. Tamper deterrent formulations (TDF) for other drugs of abuse, including stimulants and sedatives are also in various stages of development. Three major challenges face the development of TDF: the increased sophistication of the tampering methods used by abusers, the ambiguity of the regulatory requirements for labeling and marketing and the exaggerated expectations of what these formulations can deliver. This review details the approaches used by pharmaceutical manufacturers to impart tamper deterrent features into their formulations; the in vitro and in vivo tests that have been proposed or used to assess the performance of TDF; and the current regulatory landscape.

Fentanyl buccal tablet for the treatment of breakthrough pain: pharmacokinetics of buccal mucosa delivery and clinical efficacy.

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

A study of the pharmacodynamic differences between immediate and extended release bumetanide formulations.

Optimized bumetanide extended (ER) and immediate release (IR) formulations were developed using fluid bed layering and coating techniques. We postulated that the ER bumetanide formulation would have more effective and sustained diuretic and saluretic effects than IR. The diuretic/saluretic effects of both formulations were measured in rabbits (n=8) for two days after dosing with 1mg/kg bumetanide. During the first day, both formulations produced 2-3 times more urine volume and sodium excretion than baseline. In the first 24h, despite less bumetanide excretion from the ER formulation (101+/-13.9microg/kg compared to 146+/-14.6microg/kg for the IR formulation; P<0.04); the ER formulation produced diuresis and natriuresis that was equivalent to that of the IR formulation. In contrast, urine production in the IR formulation group fell below that of placebo controls on day 2. During the second day, the ER formulation was noted to produce persistent bumetanide excretion; the diuretic and natriuretic effects were not statistically significant from baseline control. We speculate that the decrease in response to bumetanide observed especially for the IR formulation during the second day may be due to the activation of compensatory counter-regulatory homeostatic mechanism(s). We conclude that the ER formulation had similar diuretic/saluretic effects but better drug excretion to urine production efficiencies than the IR formulation in the healthy rabbit model. The ER formulation, while providing comparable diuretic/saluretic effect to the IR formulation, offers the advantage of avoiding the initial, rapid and robust diuretic effect experienced with the IR formulations. Taken together, the data provide sufficient basis to warrant further investigation and refinement of our ER bumetanide formulation in humans.