Dietary Patterns and Risk of Obesity and Early Childhood Caries in Australian Toddlers: Findings from an Australian Cohort Study.

We examined associations between dietary patterns at 12 months, characterised using multiple methodologies, and risk of obesity and early childhood caries (ECC) at 24-36 months. Participants were Australian toddlers (n = 1170) from the Study of Mothers' and Infants' Life Events affecting oral health (SMILE) birth cohort. Principal Components Analysis (PCA) and the Dietary Guideline Index for Children and Adolescents (DGI-CA) were applied to dietary intake data (1, 2 or 3-days) at 12 months, and regression analysis used to examine associations of dietary patterns with body mass index Z-score and presence of ECC at 24-36 months. Two dietary patterns were extracted using PCA: family diet and cow's milk and discretionary combination. The mean DGI-CA score was 56 ± 13 (out of a possible 100). No statistically significant or clinically meaningful associations were found between dietary pattern or DGI-CA scores, and BMI Z-scores or ECC (n = 680). Higher cow's milk and discretionary combination pattern scores were associated with higher energy and free sugars intakes, and higher family diet pattern scores and DGI-CA scores with lower free sugars intakes. The association between dietary patterns and intermediate outcomes of free sugars and energy intakes suggests that obesity and/or ECC may not yet have manifested, and thus longitudinal investigation beyond two years of age is warranted.

ESUR recommendations for MR imaging of the sonographically indeterminate adnexal mass: an update.

An update of the 2010 published ESUR recommendations of MRI of the sonographically indeterminate adnexal mass integrating functional techniques is provided. An algorithmic approach using sagittal T2 and a set of transaxial T1 and T2WI allows categorization of adnexal masses in one of the following three types according to its predominant signal characteristics. T1 'bright' masses due to fat or blood content can be simply and effectively determined using a combination of T1W, T2W and FST1W imaging. When there is concern for a solid component within such a mass, it requires additional assessment as for a complex cystic or cystic-solid mass. For low T2 solid adnexal masses, DWI is now recommended. Such masses with low DWI signal on high b value image (e.g. > b 1000 s/mm2) can be regarded as benign. Any other solid adnexal mass, displaying intermediate or high DWI signal, requires further assessment by contrast-enhanced (CE)T1W imaging, ideally with DCE MR, where a type 3 curve is highly predictive of malignancy. For complex cystic or cystic-solid masses, both DWI and CET1W-preferably DCE MRI-is recommended. Characteristic enhancement curves of solid components can discriminate between lesions that are highly likely malignant and highly likely benign. KEY POINTS: • MRI is a useful complementary imaging technique for assessing sonographically indeterminate masses. • Categorization allows confident diagnosis in the majority of adnexal masses. • Type 3 contrast enhancement curve is a strong indicator of malignancy. • In sonographically indeterminate masses, complementary MRI assists in triaging patient management.

Perceptions of UK medical graduates' preparedness for practice: a multi-centre qualitative study reflecting the importance of learning on the job.

BACKGROUND: There is evidence that graduates of different medical schools vary in their preparedness for their first post. In 2003 Goldacre et al. reported that over 40% of UK medical graduates did not feel prepared and found large differences between graduates of different schools. A follow-up survey showed that levels of preparedness had increased yet there was still wide variation. This study aimed to examine whether medical graduates from three diverse UK medical schools were prepared for practice. METHODS: This was a qualitative study using a constructivist grounded theory approach. Prospective and cross-sectional data were collected from the three medical schools.A sample of 60 medical graduates (20 from each school) was targeted. They were interviewed three times: at the end of medical school (n = 65) and after four (n = 55) and 12 months (n = 46) as a Year 1 Foundation Programme doctor. Triangulated data were collected from clinicians via interviews across the three sites (n = 92). In addition three focus groups were conducted with senior clinicians who assess learning portfolios. The focus was on identifying areas of preparedness for practice and any areas of lack of preparedness. RESULTS: Although selected for being diverse, we did not find substantial differences between the schools. The same themes were identified at each site. Junior doctors felt prepared in terms of communication skills, clinical and practical skills and team working. They felt less prepared for areas of practice that are based on experiential learning in clinical practice: ward work, being on call, management of acute clinical situations, prescribing, clinical prioritisation and time management and dealing with paperwork. CONCLUSIONS: Our data highlighted the importance of students learning on the job, having a role in the team in supervised practice to enable them to learn about the duties and responsibilities of a new doctor in advance of starting work.

The adnexal incidentaloma: a practical approach to management.

There has been explosive growth in the utilization of cross-sectional imaging studies in the evaluation of patients with known or suspected abdominal and pelvic pathology. These imaging studies have led to a veritable epidemic of incidentally detected adnexal masses in both oncology and non-oncology patient populations that in the past remained undiscovered. In this commentary we provide some guidance and practical advice for further investigation and management of the adnexal incidentaloma.

Detection of diethylene glycol adulteration in propylene glycol--method validation through a multi-instrument collaborative study.

Four portable NIR instruments from the same manufacturer that were nominally identical were programmed with a PLS model for the detection of diethylene glycol (DEG) contamination in propylene glycol (PG)-water mixtures. The model was developed on one spectrometer and used on other units after a calibration transfer procedure that used piecewise direct standardization. Although quantitative results were produced, in practice the instrument interface was programmed to report in Pass/Fail mode. The Pass/Fail determinations were made within 10s and were based on a threshold that passed a blank sample with 95% confidence. The detection limit was then established as the concentration at which a sample would fail with 95% confidence. For a 1% DEG threshold one false negative (Type II) and eight false positive (Type I) errors were found in over 500 samples measured. A representative test set produced standard errors of less than 2%. Since the range of diethylene glycol for economically motivated adulteration (EMA) is expected to be above 1%, the sensitivity of field calibrated portable NIR instruments is sufficient to rapidly screen out potentially problematic materials. Following method development, the instruments were shipped to different sites around the country for a collaborative study with a fixed protocol to be carried out by different analysts. NIR spectra of replicate sets of calibration transfer, system suitability and test samples were all processed with the same chemometric model on multiple instruments to determine the overall analytical precision of the method. The combined results collected for all participants were statistically analyzed to determine a limit of detection (2.0% DEG) and limit of quantitation (6.5%) that can be expected for a method distributed to multiple field laboratories.

Clinical utility of image-guided peritoneal and omental biopsy.

Image-guided core biopsy of the omentum and peritoneum was described a decade ago and has since been validated in a number of large studies as a safe and effective means of providing a tissue diagnosis in patients with undiagnosed peritoneal disease. Some studies have addressed its ability for determining whether peritoneal infiltration and/or omental masses in patients with prior malignancy represent recurrent disease or a new disease process. Others have focused on the specific issue of women suspected to have advanced peritoneal carcinomatosis from ovarian or primary peritoneal cancer where the primary management of the patient is directed by the tissue diagnosis. The initial management of many of these women, especially those with advanced disease or substantial comorbidity, is with primary chemotherapy. With current clinical trials for ovarian cancer directed to specific morphological subtypes of the disease, image-guided core biopsy offers a rapid and well tolerated nonsurgical means of providing this information. In this Review, we discuss the technique and its clinical applications, and critically examine the currently available alternative options.

ESUR guidelines: ovarian cancer staging and follow-up.

OBJECTIVE: To design clear guidelines for the staging and follow-up of patients with ovarian cancer, and to provide the radiologist with a framework for use in multidisciplinary conferences. METHODS: Guidelines for ovarian cancer staging and follow-up were defined by the female imaging subcommittee of the ESUR (European Society of Urogenital Radiology) based on the expert consensus of imaging protocols of 12 leading institutions and a critical review of the literature. RESULTS: Computed tomography (CT) with coverage of the base of the lungs to the inguinal region is regarded as the imaging technique of choice for preoperative staging. Critical diagnostic criteria are presented and the basis for a structured report for preoperative staging is outlined. Following primary treatment for ovarian cancer, clinical assessment and CA-125 are routinely used to monitor patients. For suspected recurrence, CT remains the imaging modality of choice, with positron emission tomography (PET)/CT emerging as the optimal imaging technique for suspected recurrence, particularly in patients with negative CT or magnetic resonance imaging (MRI). CONCLUSIONS: CT is the imaging modality of choice for preoperative staging and detection of recurrence in patients with ovarian cancer.

MR imaging of the sonographically indeterminate adnexal mass.

Magnetic resonance (MR) imaging of the sonographically indeterminate adnexal mass can be used to guide patient care and reduce the costs of investigation and treatment. Most indeterminate masses result from common benign conditions, and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women in whom indeterminate masses are malignant, use of MR imaging rather than a "wait and watch" strategy of interval re-examination with ultrasonography offers a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment that direct a problem-solving, tailored approach based on signal characteristics and morphology.

Recent EORTC and MRC UK studies: implications for imaging ovarian cancer.

For many years the primary management of newly diagnosed advanced ovarian cancer has been cytoreductive surgery followed by chemotherapy, and the mainstay of follow-up of treated women has been serial assay of serum CA-125. The findings of 2 recent research protocols have a significant effect on these aspects of management.

ESUR guidelines for MR imaging of the sonographically indeterminate adnexal mass: an algorithmic approach.

A significant proportion of adnexal masses detected by sonography are indeterminate. Either their organ of origin is uncertain or it is unclear whether their nature is benign or malignant. MR imaging of the sonographically indeterminate adnexal mass can resolve most of these uncertainties. Most indeterminate masses result from common benign conditions and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women whose masses are malignant, use of MR imaging rather than a 'wait and watch' strategy of repeat ultrasound (US) results in a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment which direct an algorithmic and problem-solving approach based on signal characteristics and morphology. MR imaging should provide a more timely diagnosis and, thereby, guide the management of the patient with reduced costs of investigation and treatment.

Screening of heparin API by near infrared reflectance and Raman spectroscopy.

Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin powder samples obtained from several foreign and domestic suppliers were measured. Both the NIR and Raman spectra of individual heparin API powder samples were correlated with sample compositions determined from response corrected relative peak areas of the capillary electropherograms of the samples using a partial least squares (PLS) regression model. Twenty-eight sample spectra were used to develop PLS models for the three major sample components; heparin, oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS models were then used to successfully predict the compositions of 41 additional heparin samples. The success of these rapid, nondestructive technologies to identify contamination of heparin with OSCS demonstrates the potential of spectroscopy and chemometrics for screening of processed raw materials. These technologies are meant for screening purposes and not meant to replace either of the methods (capillary electrophoresis and NMR) currently required by USP and FDA.

Near infrared spectroscopy of magnesium stearate hydrates and multivariate calibration of pseudopolymorph composition.

Samples of magnesium stearate monohydrate and dihydrate were used to prepare standard mixtures of known pseudopolymorphic composition. Near infrared spectra (NIR) of the standard mixtures were measured to develop multivariate calibration models for the pseudopolymorphic composition of magnesium stearate by partial least squares (PLS) regression. Magnesium stearate hydrate compositions of the standard mixtures were compared against the hydrate composition based on thermogravimetric analysis (TGA). The mixture compositions determined from TGA mass loss on drying (LOD) measurements were found to be inaccurate. PLS regression was applied to the TGA thermograms of the standard mixtures to generate more accurate reference values, and this model was then applied to a set of validation samples. Application of the NIR PLS model to the validation sample set resulted in precise estimates of sample pseudopolymorphic composition when compared to the TGA PLS reference values. The NIR PLS model was found to be more sensitive than TGA LOD to small quantities of hydrates, and the TGA PLS model was also found to be more sensitive that TGA LOD. The results demonstrate the challenges and opportunities that arise when rapid, nondestructive spectroscopic methods depend on insensitive or inaccurate reference methods for development of multivariate calibration models.

Delayed release tablet dissolution related to coating thickness by terahertz pulsed image mapping.

Delayed release dosage forms such as Asacol employ coatings that are engineered to breakdown and release the drug topically at the nominal pH of the lower intestinal tract. Asacol tablets were found to dissolve in an erratic fashion when they are dissolved in buffers below pH 7 which can occur naturally. In this study Terahertz pulsed imaging (TPI) was used to accurately map the coating thickness of a group of Asacol tablets that were subsequently dissolved using the USP method at pH 6.8. The mean dissolution times were found to correlate with the average coating thickness measured over all surfaces. Thickness values for a single randomly selected face did not correlate well with the dissolution results. The speed and ease of TPI mapping may make it an attractive replacement for wet dissolution testing both in product development and eventually for process analysis.

Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension nasal spray formulations: a progress report.

PURPOSE: This study was conducted to evaluate the feasibility of using Raman chemical imaging (i.e., Raman imaging microspectroscopy) to establish chemical identity, particle size and particle size distribution (PSD) for a representative corticosteroid in aqueous nasal spray suspension formulations. MATERIALS AND METHODS: The Raman imaging PSD protocol was validated using polystyrene (PS) microsphere size standards (NIST-traceable). A Raman spectral library was developed for the active and inactive compounds in the formulation. Four nasal sprays formulated with beclomethasone dipropionate (BDP) ranging in size from 1.4 to 8.3 microm were imaged by both Raman and brightfield techniques. The Raman images were then processed to calculate the PSD for each formulation. RESULTS: Within each region examined, active pharmaceutical ingredient (API) particles are unambiguously identified and the total number of those particles, particle size and PSD of API free of excipients and PSD of API particles adhered to other excipients are reported. CONCLUSIONS: Good statistical agreement is obtained between the reported and measured sizes of the PS microspheres. BDP particles were clearly distinguishable from those of excipients. Raman chemical imaging (RCI) is able to differentiate between and identify the chemical makeup of multiple components in complex BDP sample and placebo mixtures. The Raman chemical imaging method (coupled Raman and optical imaging) shows promise as a method for characterizing particle size and shape of corticosteroid in aqueous nasal spray suspension formulations. However, rigorous validation of RCI for PSD analysis is incomplete and requires additional research effort. Some specific areas of concern are discussed.

Image guided biopsy in the management of cancer of the ovary.

When used in the context of multidisciplinary team discussion, image guided biopsy using ultrasound (US) or computed tomography (CT) guidance is of value in planning management of women with suspected ovarian cancer and peritoneal carcinomatosis (PC) of uncertain aetiology. It is essential in women believed to have ovarian cancer but with poor performance status or with advanced disease believed beyond the scope of primary cytoreductive surgery for whom staging surgical pathology will not be obtained. It provides a site-specific primary tumour diagnosis in 93% of cases and it should replace diagnostic laparoscopy or laparotomy for this purpose. It allows provision of primary (neoadjuvant) chemotherapy based on a firm histological diagnosis. It is mandatory in women with a history of cancer whose metastases may mimic ovarian cancer (e.g. breast, GI tract, melanoma). More women with prior breast cancer who re-present with peritoneal cancer will have a new gynaecological primary than recurrence of their original primary tumour; the two options require radically different therapies. Finally it is a valuable problem solving tool in situations of diagnostic uncertainty, e.g. unusual imaging patterns of disease such as PC with bilateral solid ovarian masses or non-enlarged ovaries and with an unusual tumour marker profiles suggesting primary tumours outwith the ovary. The technique is simple, safe and effective and can be combined with palliative drainage of ascites at the same procedure.

Quality assessment of internet pharmaceutical products using traditional and non-traditional analytical techniques.

This work investigated the use of non-traditional analytical methods to evaluate the quality of a variety of pharmaceutical products purchased via internet sites from foreign sources and compared the results with those obtained from conventional quality assurance methods. Traditional analytical techniques employing HPLC for potency, content uniformity, chromatographic purity and drug release profiles were used to evaluate the quality of five selected drug products (fluoxetine hydrochloride, levothyroxine sodium, metformin hydrochloride, phenytoin sodium, and warfarin sodium). Non-traditional techniques, such as near infrared spectroscopy (NIR), NIR imaging and thermogravimetric analysis (TGA), were employed to verify the results and investigate their potential as alternative testing methods. Two of 20 samples failed USP monographs for quality attributes. The additional analytical methods found 11 of 20 samples had different formulations when compared to the U.S. product. Seven of the 20 samples arrived in questionable containers, and 19 of 20 had incomplete labeling. Only 1 of the 20 samples had final packaging similar to the U.S. products. The non-traditional techniques complemented the traditional techniques used and highlighted additional quality issues for the products tested. For example, these methods detected suspect manufacturing issues (such as blending), which were not evident from traditional testing alone.