Translational use of homing peptides: Tumor and placental targeting.

HYPOTHESIS: Tissue-specific homing peptides have been shown to improve chemotherapeutic efficacy due to their trophism for tumor cells. Other sequences that selectively home to the placenta are providing new and safer therapeutics to treat complications in pregnancy. Our hypothesis is that the placental homing peptide RSGVAKS (RSG) may have binding affinity to cancer cells, and that insight can be gained into the binding mechanisms of RSG and the tumor homing peptide CGKRK to model membranes that mimic the primary lipid compositions of the respective cells. EXPERIMENTS: Following cell culture studies on the binding efficacy of the peptides on a breast cancer cell line, a systematic translational characterization is delivered using ellipsometry, Brewster angle microscopy and neutron reflectometry of the extents, structures, and dynamics of the interactions of the peptides with the model membranes on a Langmuir trough. FINDINGS: We start by revealing that RSG does indeed have binding affinity to breast cancer cells. The peptide is then shown to exhibit stronger interactions and greater penetration than CGKRK into both model membranes, combined with greater disruption to the lipid component. RSG also forms aggregates bound to the model membranes, yet both peptides bind to a greater extent to the placental than cancer model membranes. The results demonstrate the potential for varying local reservoirs of peptide within cell membranes that may influence receptor binding. The innovative nature of our findings motivates the urgent need for more studies involving multifaceted experimental platforms to explore the use of specific peptide sequences to home to different cellular targets.

Ovarian neoplasia in adolescence: a retrospective chart review of girls with neoplastic ovarian tumors in Saudi Arabia.

BACKGROUND: Ovarian neoplasia in children and adolescents is a rare tumor. The diagnosis and management of such tumors is often difficult and delayed due to non-specific symptoms and low suspicion. Surgical management that preserves fertility and ovarian function should be the goal. OBJECTIVE: This study aimed to review the clinical presentation, tumor characteristics, and management of Saudi Arabian adolescents. METHODS: A retrospective chart review was conducted on adolescent girls aged 19 or less admitted to tow referral hospital in Riyadh, Saudi Arabia, diagnosed with adnexal mass over an 8 years' period; patients who were older than 19 were excluded. The data collected from patients' charts included age, presenting symptoms, radiologic findings, type of surgery, specialist who performed the surgery, and histopathology of the tumors. We classified patients according to age using the three WHO developmental stages: early adolescence (10-13 years old), middle adolescence (14-16 years old), and late adolescence (16-17 years old). The statistical study used SPSS version 18.0 to determine the data's frequency, distributions, and means (SPSS Inc., Chicago, IL). RESULTS: We analyzed 164 patients, between 10 and 19 years old, admitted to two hospitals between 2009 and 2017. We found that 85% of these patients underwent surgery for adnexal mass removal, and 90.2% were symptomatic or emergency cases. The majority of our patients were post-menarche (96.95%), and were between the ages of 14 and 19. The most common surgical procedure for tumor removal was laparoscopic cystectomy (74.4%). An adnexal mass with a solid component on ultrasound is the most commonly found indicator of malignancy. The majority of tumors were benign (32.3%). Germ cell tumors were the most common (68.7%) malignant tumor, and yolk sac tumors were the most common subgroup of germ cell tumors. When managed by a gynecologist, surgical intervention can be a successful method of preserving fertility. CONCLUSIONS: Our results confirm that the majority of neoplastic ovarian tumors in children and adolescents are benign, and surgical intervention can be used to maintain fertility, especially when managed by a gynecologist. This is one of the largest reported series and the first from our area.

Kimura Disease: An Unusual Presentation of Parotid Mass in a Sickle Cell Disease Patient.

Kimura disease (KD) is a rare benign chronic inflammatory condition of unknown cause, usually affecting young men of the Asian race. It is frequently associated with nephrotic syndrome. In this report, we present an uncommon case of KD in a 40-year-old Saudi man with sickle cell disease who presented with swelling on the right side of his face. CT scan of the head and neck showed the asymmetrical appearance of both parotid glands: the right side appeared heterogeneously enlarged, with adjacent moderate-to-significant fat stranding. Histologically, hyperplastic changes in lymphoid tissue were observed. The patient underwent superficial parotidectomy and was then followed up till the healing of the surgical site with no complications.

The Prevalence of Depression and Anxiety in Post-bariatric Surgery Patients at King Khalid University Hospital, Riyadh.

Background Obesity negatively impacts mental and physical health and is a leading cause of disease worldwide. Obesity affects 33% of Saudi adults, with 10% being morbidly obese (body mass index, BMI >40 kg/m2). This study explored the association between bariatric surgery (BS) and a predisposition or exacerbation of depressive and anxiety symptoms. Material and methods A cross-sectional study of patients who underwent bariatric surgery at the King Khalid University Hospital in Riyadh, Saudi Arabia, was conducted between February 2016 and December 2021. The patients were contacted by phone to complete a self-administered questionnaire on demographic information, chronic medical diseases, psychiatric diseases, body mass index, and type of bariatric surgery. In addition, they completed the patient health questionnaire-9 (PHQ-9) and general anxiety disorder-7 (GAD-7) questionnaire to screen for patients' depression and anxiety symptoms. Results The findings of the 367 BS patients showed that 20.7% of the patients were considered to have mild anxiety, 11.2% had moderate anxiety, and 8.7% had high anxiety levels. However, regarding depression, 46.9% had extremely low levels of depression, followed by mild depression in 29.4% and moderate depression in 11.2%. Furthermore, another 8.2% of BS patients had moderately high depression levels, and 4.4% had severe depression. The anxiety and depression levels of the patients in this study did not show any statistically significant changes postoperatively in the short, medium, or long term. On the other hand, almost all of the patients 97% who underwent bariatric surgery were satisfied with the outcome of their surgery. Conclusion Few BS patients had high symptoms of depression and anxiety. We recommend pre- and postoperative psychiatric assessment for all bariatric surgery patients as surgical protocol.

Diagnostic Reliability of Ultrasound Compared to Magnetic Resonance Cholangiopancreatography and Endoscopic Retrograde Cholangiopancreatography in the Detection of Obstructive Jaundice: A Retrospective Medical Records Review.

Background Challenges in the diagnosis of obstructive jaundice include locating the level of obstruction, knowing the cause of obstruction, and differentiating between benign and malignant causes. Imaging plays a significant role in detecting the causes of obstruction. Radiologists aim to diagnose biliary obstruction, its level, extent, and probable causes to determine the appropriate treatment for each case.  Methods Our study is a retrospective medical record review study. It included 150 patients who had ultrasound (US) diagnosis of biliary obstruction and underwent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in King Fahad Specialist Hospital, Buraidah. The patients' medical records have been reviewed to measure the sensitivity and specificity of US, MRCP, and ERCP.  Results Statistical analysis of the data showed that the sensitivity of US in detecting the most common cause of biliary obstruction, common bile duct (CBD) stone, was 26.6%, while the specificity was 100%. Comparing this sensitivity of US in detecting CBD stones to that of MRCP and ERCP, we obtained the following: US, 26.6%; MRCP, 62.9%; and ERCP, 62.4%. Although US was the least sensitive for detecting CBD stones, its specificity in this detection was 100%, while MRCP was 63.6%, and ERCP was 55.2%. Conclusion  US is the best initial step for the diagnosis of biliary obstruction. However, MRCP and ERCP are more sensitive in detecting CBD stones compared to US. Also, compared to US, they have shown higher percentages in all aspects of detection: level, cause, and extent of biliary obstruction.

Intraventricular Tigecycline as a Last Resort Therapy in a Patient with Difficult-to-Treat Healthcare-Associated Acinetobacter baumannii Ventriculitis: a Case Report.

Healthcare-associated ventriculitis and meningitis is a common complication in patients who suffer from head trauma or have undergone a neurosurgery. Healthcare-associated ventriculitis and meningitis is associated with significant morbidity and mortality. Complications of healthcare-associated ventriculitis and meningitis include persistent vegetative state, moderate and severe disability, and death. Acinetobacter baumannii is the causative pathogen in 3.6-11.2% of cases of healthcare-associated ventriculitis and meningitis. Cases of difficult-to-treat healthcare-associated A. baumannii ventriculitis and meningitis are being reported more frequently. However, in most of these cases, a combination of intravenous (IV) and intraventricular (IVT)/intrathecal colistin achieves good therapeutic outcome. This report describes a clinical case of difficult-to-treat healthcare-associated A. baumannii ventriculitis. The A. baumannii strain was sensitive to colistin and trimethoprim-sulfamethoxazole, intermediate to tigecycline, and resistant to other antibiotics. While colistin was the drug of choice in our case, the patient developed anaphylactoid reaction during the IV administration of the loading dose of colistin, which mandated us to discontinue colistin and complicated the treatment of our patient. The patient did not respond to a combination of IV antibiotics that included meropenem, trimethoprim-sulfamethoxazole, and tigecycline. However, when IVT tigecycline was added as a last-resort therapeutic option, the patient's ventriculitis dramatically improved, and the patient was discharged from the hospital. Physicians who treat patients with healthcare-associated A. baumannii ventriculitis might resort to IVT tigecycline when they run out of therapeutic options.

Low-risk gestational trophoblastic neoplasia: A single-center experience from Saudi Arabia.

OBJECTIVE: To report our single-center experience in terms of patient clinical characteristics, treatment outcomes, and chemotherapy-related toxicities in patients with low-risk gestational trophoblastic neoplasia (GTN). MATERIALS AND METHODS: A retrospective cross-sectional study (2008-2013) was conducted at a tertiary health-care hospital in Saudi Arabia. Forty-four (n = 44) patients met the inclusion criteria for low-risk GTN. Methotrexate (MTX) was administered in a 5-day regimen: 0.3-0.5mg/kg intravenously (IV) daily for 5 days every 2 weeks (maximum 25mg per dose). Actinomycin D (ActD) was administered 1.25mg/m2 pulsed IV every 2 weeks. RESULTS: The majority of patients had molar pregnancy as the antecedent event (86%), developed GTN within the first 4 months after the initial evacuation (93.2%), had human chorionic gonadotropin levels between 1,000 and 10,000 mIU/dL (36.3%), and had the World Health Organization prognostic scores from 0 to 2 (48.7%). Only 38 patients accepted treatment with chemotherapy. A total of 37 patients received first-line MTX; 34 patients of them achieved complete remission (CR, 92%). The three patients who developed MTX resistance were salvaged with sequential ActD and all achieved CR of 100%. Only one patient received first-line ActD and achieved CR. The overall survival as well as cure rate for all patients with low-risk GTN was 100%. No patient developed MTX-related hepatic toxicity or ActD-related blister formation. No severe adverse effects occurred. CONCLUSION: Our 5-day IV MTX regimen was highly effective in treating patients with low-risk GTN, with CR rate of 92% and no severe toxicity. Primary and sequential ActD therapy appears to be very effective.

An Extremely Giant Ovarian Mucinous Cystadenoma.

Ovarian mucinous cystadenomas are cystic neoplasms lined by mucin-producing epithelial cells. They are mostly benign (80%) and frequently asymptomatic at early stages. The average diameter of ovarian mucinous cystadenomas ranges from 15 to 30 cm. Herein, we report the case of a giant benign ovarian mucinous cystadenoma in a 53-year-old postmenopausal woman. The patient presented with a very huge pelvi-abdominal distention that started ten months ago and was progressively increasing in size. It was associated with on-off abdominal pain, nausea and urinary retention. The case was discussed with a multidisciplinary team. Subsequently, the patient was consented for exploratory laparotomy. The origin of the mass was identified to be the right ovary, and right salpingo-oophorectomy was done. The resected mass measured 73x51x42 cm and weighed 108 kg. The left ovary had a multilocular mass of 15 cm in diameter, and left salpingo-oophorectomy was successively performed. There was no ascites. Histopathological examination confirmed the diagnosis of bilateral benign mucinous cystadenoma. At a postoperative 9-month follow-up in the outpatient clinic, the patient showed up in good condition without evidence of recurrence. To the best of our knowledge, we report the largest benign ovarian cyst in Saudi Arabia, and one of the largest (probably the third) in the English medical literature. It is technically feasible to manage an extremely large-sized benign mass with satisfactorily perioperative outcomes. This should be done through a multidisciplinary approach that demands an orchestrated collaboration between different specialists to yield an optimized perioperative care.

Defining optimal dosing of ciprofloxacin in patients with septic shock.

BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS: We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. CONCLUSIONS: In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.

Effect of vitamin D3 supplementation in pregnancy on risk of pre-eclampsia - Randomized controlled trial.

BACKGROUND: Vitamin D plays pivotal role in decidualization and implantation of the placenta. Recent researches have shown that low level of vitamin D3 "25-hydroxyvitamin D (25[OH]D)" in serum is a risk factor for pre-eclampsia. Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia. The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level. METHOD: An open labelled randomized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015. Patients with age less than 20 years or more than 40 years, pregnancy with fetal anomalies, history of hypertension, pre-eclampsia, recurrent miscarriage, chronic renal or hepatic disease and malignancy were excluded from the study. Serum 25[OH]D was analysed during the first trimester (between 6 and 12 weeks of pregnancy). Patients with vitamin D3 deficiency (serum levels <25 nmol/L) were included in the study and randomized for vitamin D3 supplementation 400 IU (Group 1) versus 4000 IU (Group 2). Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level. RESULTS: Of 179 gravidae enrolled, 164 completed the trial. Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL (p > 0.0001). The relative risk reduction (RRR) for attaining ≥75 nmol/L before delivery was significantly higher (RRR 93.2 [CI 79-98] when treated with 4000 IU. The total incidence of pre-eclampsia in the study population was 4.3%. In comparison to group 1, the group 2 reported fewer pre-eclampsia events during the study period (8.6% versus 1.2%; p < 0.05). The total number of IUGRs was lesser in the group 2 (9.6%) versus group 1 (22.2%); p = 0.027. However, other obstetric outcomes were comparable between both groups. CONCLUSION: Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner. However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group.

Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis.

BACKGROUND: Sustained low-efficiency dialysis (SLED), is increasingly being used in intensive care units (ICUs) but studies informing drug dosing for such patients is lacking. OBJECTIVE: To describe the population pharmacokinetics (PKs) of piperacillin/tazobactam in critically ill adults receiving SLED and to provide dosing recommendations. METHODS: This prospective population PK study was conducted in adult ICU patients prescribed piperacillin/tazobactam while receiving SLED; 321 blood samples were obtained from 34 participants during and between approximately 50 SLED treatments for quantification of piperacillin and tazobactam concentrations in plasma. A population PK model was developed. Monte Carlo simulation was used to determine the probability of target attainment and pathogen-specific fractional target attainment at different doses. RESULTS: From a 2-compartment linear model with zero-order input, the mean (SD) clearance of piperacillin on SLED and off SLED were 4.81 (8.48) and 1.42 (1.54) L/h, respectively. Tazobactam concentrations were not sufficient for analysis. For the target of 50% fT>MIC (unbound concentrations of drug are above the minimum inhibitory concentration for >50% of the dosing interval), 3-g of piperacillin infused over 0.5 hours every 8 hours was appropriate for susceptible organisms with MIC ≤16 mg/L. For life-threatening infections where the target of 100% fT>MIC is preferred, a 9-g dose administered as a continuous infusion every 24 hours was appropriate for susceptible organisms with MIC ≤32 mg/L. CONCLUSIONS AND RELEVANCE: In critically ill patients receiving SLED, piperacillin doses need to be guided by the frequency of SLED treatments and susceptibility of the known or suspected pathogen.

Protective potential of thymoquinone against peroxynitrite induced modifications in histone H2A: In vitro studies.

Peroxynitrite (ONOO-) is a reactive oxidant involved in numerous pathological conditions. Thymoquinone (TQ) is an active constituent of Nigella sativa and is reported to have anti-disease activities, but its role on ONOO- has never been investigated. This study was undertaken to investigate the role of TQ on ONOO--induced damage of histone-H2A. Our novel data showed TQ significantly inhibited ONOO--induced oxidative damage in histone-H2A. ONOO- induces UV-hypochromicity of histone-H2A, whereas TQ reversed this effect to hyperchromicity. Tyrosine fluorescence was significantly reduced by ONOO- and was significantly increased upon TQ treatment. TQ reduces ONOO--induced hydrophobicity in histone-H2A and also reduces thermal stability of ONOO--histone H2A complex. SDS-PAGE of native histone-H2A showed a single band, which disappeared when treated with ONOO- alone. This changed was retained when protein samples were treated with TQ. Similar protective effects of TQ were found when protein carbonyl contents were estimated. In conclusion, this is the first study that shows the potential of TQ against ONOO--induced damaged of histone-H2A. TQ inhibits oxidative modification of tyrosine, lysine, arginine, proline and threonine in histone-H2A. These results have importance for the development of novel therapeutic strategies for the treatment of disorders, where ONOO- plays a role.

Maximally effective dosing regimens of meropenem in patients with septic shock.

OBJECTIVES: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. METHODS: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. RESULTS: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. CONCLUSIONS: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.

Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections.

We sought to describe the population pharmacokinetics of tigecycline in critically ill patients and to determine optimized dosing regimens of tigecycline for different bacterial infections. This prospective study included 10 critically ill patients given a standard dose of tigecycline. Blood samples were collected during one dosing interval and were analyzed using validated chromatography. Population pharmacokinetics and Monte Carlo dosing simulations were undertaken using Pmetrics. Three target exposures, expressed as ratios of the 24-h area under the curve to MICs (AUC0-24/MIC), were evaluated (≥17.9 for skin infections, ≥6.96 for intra-abdominal infections, ≥4.5 for hospital-acquired pneumonia). The median age, total body weight, and body mass index (BMI) were 67 years, 69.1 kg, and 24.7 kg/m2, respectively. A two-compartment linear model best described the time course of tigecycline concentrations. The parameter estimates (expressed as means ± standard deviations [SD]) from the final model were as follows: clearance (CL), 7.50 ± 1.11 liters/h; volume in the central compartment, 72.50 ± 21.18 liters; rate constant for tigecycline distribution from the central to the peripheral compartment, 0.31 ± 0.16 h-1; and rate constant for tigecycline distribution from the peripheral to the central compartment, 0.29 ± 0.30 h-1 A larger BMI was associated with increased CL of tigecycline. Licensed doses were found to be sufficient for Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus for an AUC0-24/MIC target of 4.5 or 6.96. For a therapeutic target of 17.9, an increased tigecycline dose is required, especially for patients with higher BMI. The dosing requirements of tigecycline differ with the indication, with pathogen susceptibility, and potentially with patient BMI.

Inguinal lymph node presenting as the delayed site of metastasis in early stage endometrial carcinoma: Case report.

INTRODUCTION: Inguinal lymph nodes are the frequent sites of metastasis for malignant lymphoma, squamous cell carcinoma of anal canal, vulva and penis, malignant melanoma and squamous cell carcinoma of skin over lower extremities or trunk. Anatomically, endometrial carcinoma is less likely to spread to the superficial or deep inguinal lymph nodes, thus metastatic involvement of these lymph nodes can easily be overlooked. CASE PRESENTATION: Here-in we report a case of a 65-year old Saudi morbid obese female, who presented with left inguinal lymphadenopathy as initial delayed site of metastasis almost 19 months after the initial treatment for FIGO IA endometrial carcinoma. Patient underwent left inguinal lymph node dissection. Histopathology confirmed metastatic endometrial adenocarcinoma, positive for cytokeratin (CK-7), estrogen receptor (ER) and progesterone receptors (PR), negative for CK-20 and CDX2. Following the post-surgery recovery, she was given extended field radiation therapy to para-aortic, pelvis and bilateral inguinal lymph nodes with concurrent cisplatin chemotherapy followed by high dose rate brachytherapy. CONCLUSION: Inguinal lymph nodes as delayed site of metastasis in early endometrial carcinoma is extremely rare entity. Incorporation of FDG-PET during the preoperative screening of inguinal nodes may be helpful. The impact of lymph node dissection and adjuvant radiation therapy on survival needs to be established.

Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.

The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1 A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

Tubo-ovarian abscess in non sexually active adolescents.

A tubo-ovarian abscess is a rare presentation in non-sexually active adolescents; only 11 cases have been reported in the literature. Variable approaches for diagnosis and management are described. We present a 19-year-old, non-sexually active, medically free girl, who had an abdominopelvic mass with abdominal pain and vomiting followed by fever. She had a confusing presentation of malignancy versus tuberculosis, with the help of imaging, diagnosis and treatment with percutaneous drainage, conservative treatment was achieved. Diagnosis of a tubo-ovarian abscess is difficult in non-sexually active adolescents, a high clinical index of suspicion is important as misdiagnosis may lead to radical and aggressive management, conservative management is possible in many of these patients.

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients.

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2 A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Attitudes of Patients in Developing Countries Toward Participating in Clinical Trials: A Survey of Saudi Patients Attending Primary Health Care Services.

OBJECTIVES: Clinical trials are experimental projects that include patients as subjects. A number of benefits are directly associated with clinical trials. Healthcare processes and outcomes can be improved with the help of clinical trials. This study aimed to assess the attitudes and beliefs of patients about their contribution to and enrolment in clinical trials. METHODS: A cross-sectional study design was used for data collection and analysis. A questionnaire was developed with six categories to derive effective outcomes. RESULTS: Of the 2000 participants approached to take part in the study, 1081 agreed. The majority of the study population was female, well educated, and unaware of clinical trials. Only 324 subjects (30.0%) had previously agreed to participate in a clinical trial. The majority (87.1%) were motivated to participate in clinical trials due to religious aspects. However, fear of any risk was the principal reason (79.8%) that reduced their motivation to participate. CONCLUSIONS: The results of this study revealed that patients in Saudi Arabia have a low awareness and are less willing to participate in clinical trials. Different motivational factors and awareness programs can be used to increase patient participation in the future.

Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients.

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (≥40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean ± standard deviation (SD) age, weight, and BMI were 49 ± 15.9 years, 95 ± 22.0 kg, and 33 ± 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean ± SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 ± 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 ± 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 ± 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 ± 12.24 liters h(-1) Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V1, dose adjustment based on CLCR appears to be more important than patient BMI.