Country learning on maintaining quality essential health services during COVID-19 in Timor-Leste: a qualitative analysis.

OBJECTIVE: This case study examines the enabling factors, strengths, challenges and lessons learnt from Timor-Leste (TLS) as it sought to maintain quality essential health services (EHS) during the COVID-19 pandemic. DESIGN: A qualitative case study triangulated information from 22 documents, 44 key informant interviews and 6 focus group discussions. The framework method was used to thematically examine the factors impacting quality EHS in TLS. SETTING: National, municipal, facility levels in Baucau, Dili and Ermera municipalities in TLS. RESULTS: Based on the TLS National Health Statistics Reports, a reduction in outpatient, emergency department and primary care service delivery visits was observed in 2020 when compared with 2019. However, in contrast, maternal child health services simultaneously improved in the areas of skilled birth attendants, prenatal coverage and vitamin A distribution, for example. From the thematic analysis, five themes emerged as contributing to or impeding the maintenance of quality EHS including (1) high-level strategy for maintaining quality EHS, (2) measurement for quality and factors affecting service utilisation, (3) challenges in implementation of quality activities across the three levels of the health system, (4) the impact of quality improvement leadership in health facilities during COVID-19 and (5) learning systems for maintaining quality EHS now and for the future. CONCLUSION: The maintenance of quality EHS is critical to mitigate adverse health effects from the COVID-19 pandemic. When quality health services are delivered prior to and maintained during public health emergencies, they build trust within the health system and promote healthcare-seeking behaviour. Planning for quality as part of emergency preparedness can facilitate a high standard of care by ensuring health services continue to provide a safe environment, reduce harm, improve clinical care and engage patients, facilities and communities.

Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies.

UNLABELLED: AKT (a serine/threonine-specific protein kinase) regulates many cellular processes contributing to cytotoxic drug resistance. This study's primary objective examined the relationship between GSK2141795, an oral, pan-AKT inhibitor, and (18)F-FDG PET markers of glucose metabolism in tumor tissue to determine whether (18)F-FDG PET could be used to guide personalized dosing of GSK2141795. Biomarker analysis of biopsies was also undertaken. METHODS: Twelve patients were enrolled in 3 cohorts; all underwent dynamic (18)F-FDG PET scans and serial pharmacokinetic sampling at baseline, week 2, and week 4 with tumor biopsies before treatment and at week 4. Response was evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup criteria. Biopsy samples were analyzed for mutations and protein expression. RESULTS: GSK2141795 did not significantly influence blood glucose levels. No dose-response relationship was observed between GSK2141795 pharmacokinetics and (18)F-FDG PET pharmacodynamic measures; however, an exposure-response relationship was seen between maximum drug concentrations and maximal decrease in (18)F-FDG uptake in the best-responding tumor. This relationship also held for pharmacokinetic parameters of exposure and 1,5-anhydroglucitol (a systemic measure of glucose metabolism). Phospho-AKT upregulation at week 4 in biopsies confirmed AKT inhibition by GSK2141795. Single-agent activity was observed with a clinical benefit rate of 27% (3/11) and 30% (3/10) CA125 response in the study's platinum-resistant ovarian patients. AKT pathway activation by PIK3CA/PIK3R1 mutation did not correlate with clinical activity, whereas RAS/RAF pathway mutations did segregate with resistance to AKT inhibition. CONCLUSION: GSK2141795 demonstrated an exposure-response relationship with decreased (18)F-FDG uptake and is active and tolerable. This study's design integrating (18)F-FDG PET, pharmacokinetics, and biomarker analyses demonstrates the potential for clinical development for personalized treatment.

MRI appearances of uterine malignant mixed müllerian tumors.

OBJECTIVE: Uterine malignant mixed müllerian tumors (MMMTs) are rare aggressive tumors with a high incidence of lymphatic, peritoneal, and pulmonary metastases. Preoperative differentiation from endometrial adenocarcinoma would be beneficial because their prognoses differ. MATERIALS AND METHODS: We retrospectively reviewed MRI examinations of 51 histologically confirmed MMMTs. Tumor size, growth pattern, and imaging characteristics were recorded. Data were compared with MRI appearances of 73 endometrial adenocarcinomas. RESULTS: On T1-weighted images, MMMTs were predominantly isointense to myometrium (76%) and endometrium (71%), with heterogeneous texture in 33% of cases and hyperintense foci in 27% of cases. On T2-weighted images, 92% of MMMTs were hyperintense to myometrium and either hypointense (55%) or isointense (41%) to endometrium. In 12% of cases, large heterogeneous MMMTs obliterated uterine architecture and were aggressive in appearance, whereas in 88% of cases, the appearances were indistinguishable from those of endometrial adenocarcinoma. Significantly more MMMTs than endometrial adenocarcinomas had cervical invasion (p = 0.008) and nodal enlargement (p = 0.00008). Dynamic contrast-enhanced images (available for 19 of 51 patients) obtained at less than 1 minute after administration of contrast agent showed MMMT enhancement to be hypointense (42%; 5/12 patients) or isointense (33%; 4/12 patients) to myometrium; between 1 and 4 minutes after administration of contrast agent, tumors were hypointense (58%; 7/12 patients); and at more than 4 minutes after administration of contrast agent (n = 18), MMMTs were isointense in 56% of cases. This finding is significantly different from that for endometrial adenocarcinoma, where enhancement is less than that of myometrium in 90% of cases (p = 4 × 10⁻8). CONCLUSION: MMMTs do not have a pathognomonic MRI appearance. However, radiologic suspicion should increase in the presence of large heterogeneous infiltrative tumors or when tumoral enhancement equals or exceeds that of myometrium.

MRI demonstration of the effect of neoadjuvant radiotherapy on rectal carcinoma.

BACKGROUND AND PURPOSE: In patients with locally advanced rectal cancer, neoadjuvant long course (45-54 Gy in 25-30 fractions) chemoradiotherapy (CRT) may reduce tumour size and result in downstaging. In patients with primary resectable tumour short course (25 Gy in 5 fractions) radiotherapy (SCRT) reduces local recurrence but downstaging the disease or altering tumour size has not been described. We aimed to assess change in tumour size on MRI after SCRT or CRT. MATERIALS AND METHODS: Nineteen patients with rectal carcinoma underwent MRI before and after SCRT or CRT. In each case, tumour length and width were documented and number of locoregional lymph nodes recorded. Total mesorectal excision was performed in 15 patients and MR findings correlated with histopathology. RESULTS: Ten patients received SCRT and nine CRT. Tumour length reduced by 19% overall (15% following SCRT, 23% following CRT). Greater than 30% reduction (partial response) in maximum tumour thickness was seen in 4/10 (40%) following SCRT and 5/9 (56%) following CRT. CONCLUSIONS: Significant reduction in tumour size can be achieved with preoperative long course CRT and SCRT. This unexpected finding following SCRT has not been previously described.

Human 5-HT transporter availability predicts amygdala reactivity in vivo.

The amygdala plays a central role in fear conditioning, emotional processing, and memory modulation. A postulated key component of the neurochemical regulation of amygdala function is the neurotransmitter 5-hydroxytryptamine (5-HT), and synaptic levels of 5-HT in the amygdala and elsewhere are critically regulated by the 5-HT transporter (5-HTT). The aim of this study was to directly examine the relationship between 5-HTT availability and amygdala activity using multimodal [positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)] imaging measures in the same individuals. Healthy male volunteers who had previously undergone an [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) PET scan to determine 5-HTT availability completed an fMRI emotion recognition task. [11C]-DASB binding potential values were calculated for the amygdala using arterial input function and linear graphical (Logan) analysis. fMRI was performed on a 3T Philips Intera scanner, and data were analyzed using SPM2 (Wellcome Department Imaging Neuroscience, University College London). Percentage signal change during the task was extracted from the amygdala using MarsBaR (Brett et al., 2002). fMRI analysis revealed significant amygdala activation during the emotion recognition task. Region of interest analyses demonstrated a significant negative correlation between fMRI signal change in the left amygdala and 5-HTT availability in the left amygdala, with 5-HTT availability accounting for approximately 42% of the variability in left amygdala activity. Our novel in vivo data highlight the central importance of the serotonergic system in the responsiveness of the human amygdala during emotional processing.

Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer.

PURPOSE: Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. METHODS: Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. RESULTS: Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93. CONCLUSION: Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.

CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome.

Adrenocorticotropic hormone (ACTH)-independent hypercortisolism accounts for 15%-20% of cases of Cushing syndrome and always arises from primary adrenal disease. Computed tomographic (CT) and magnetic resonance (MR) imaging findings in 37 patients with primary adrenal Cushing syndrome were analyzed and correlated with pathologic findings. Hyperfunctioning adenomas (n = 24), together with functioning carcinomas (n = 10), accounted for 92% of cases. Adenomas had a significantly smaller mean size (3.5 vs 14.5 cm) and lower mean unenhanced CT attenuation value (11 vs 28 HU) than did carcinomas. The presence of necrosis, hemorrhage, and calcification favored a diagnosis of carcinoma. Six of 10 carcinoma patients had metastases at presentation. Two adenomas were seen within a myelolipoma, which was recognized at both CT and MR imaging due to its fat content, and two adenomas were of uncertain malignant potential. Bilateral disease--primary pigmented nodular adrenal dysplasia (PPNAD) (n = 2) and ACTH-independent macronodular adrenal hyperplasia (AIMAH) (n = 1)--had characteristic imaging features. In PPNAD, multiple tiny (2-5-mm) nodules were visible bilaterally, with no overall glandular enlargement and normal intervening adrenal tissue. In AIMAH, both glands were grossly enlarged and contained nodules up to 3 cm in diameter. Familiarity with the range of imaging appearances of the adrenal glands in primary adrenal Cushing syndrome may help establish the underlying diagnosis.