The effect of amputation level on patient mental and psychological health, prospective observational cohort study.

Background: Non-traumatic lower limb amputation is a commonly performed surgical procedure and is associated with a high prevalence of psychological morbidity including anxiety and depression. Many risk factors have been identified, including the indication for amputation, perioperative pain and sociodemographic factors. Objective: The aim of this study was to identify whether level of amputation has an impact on this psychological morbidity. Methods: A prospective observational study was conducted in a tertiary vascular unit including all adult non-traumatic amputations performed during a 6 month period. The Hospital Anxiety and Depression Scale (HADS) was used to score anxiety and depression pre and postoperatively. Results: 49 patients met the inclusion criteria (22 trans-femoral amputations (AKA) and 27 trans-tibial amputations (BKA)). HADS scores for anxiety and depression were high in both groups both pre and postoperatively. A higher level of anxiety was noted in the BKA group, significantly decreasing postoperatively (p < 0.05). No other statistically significant differences were found between the two groups. Conclusion: In non-traumatic amputations, there appears to be a higher rate of pre-operative anxiety in patients undergoing trans-tibial amputation compared with trans-femoral amputees. However, the level of amputation does not appear to have a significant effect on psychological status of patients with high rates of depression and anxiety demonstrated in both groups.

EMPTY SELLA IN A PATIENT WITH CLINICAL AND BIOCHEMICAL DIAGNOSIS OF ACROMEGALY.

Background: Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Empty sella (ES) is an anatomical condition of sella turcica that is partially or completely filled with cerebrospinal fluid mainly due to intrasellar herniation of subarachnoid space. Here, we describe a patient who presented with clinical and biochemical features of acromegaly and who had an ES on pituitary magnetic resonance imaging (MRI). Case report: A 73-year-old male patient was consulted in our clinic because of the acromegalic phenotype while planning for colorectal adenocarcinoma surgery. The patient noticed gradual enlarging of his hands, feet and nose for 30 years, but never consulted to any clinician for this reason. Serum GH was 20.6 ng/mL (normal <3 ng/mL) and IGF-1 was 531 ng/mL (normal, 69-200 ng/ml). An oral glucose tolerance test showed no suppression of GH values. T1-weighted MRI revealed an ES. 18F-FDG PET/CT and Ga-DOTATADE PET/CT did not show any finding consistent with ectopic GH secretion. Growth hormone releasing hormone (GHRH) was within the normal range (<100mg/dL). He was treated with long-acting octreotide 20 mg per 28 days. At the 6th month of treatment, serum GH and IGF-1 levels were decreased to 5.45 ng/mL and 274 ng/mL, respectively. Conclusion: The mechanism underlying the association of acromegaly and ES remains unclear. Apoplexy on existing pituitary adenoma and then formation of necrosis can proceed to ES. Since our patient did not have a history of pituitary apoplexy and we could not find any reason for secondary ES, we considered primary ES.

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Prediction of Cognitive Decline for Enrichment of Alzheimer's Disease Clinical Trials.

BACKGROUND: A key issue to Alzheimer's disease clinical trial failures is poor participant selection. Participants have heterogeneous cognitive trajectories and many do not decline during trials, which reduces a study's power to detect treatment effects. Trials need enrichment strategies to enroll individuals who are more likely to decline. OBJECTIVES: To develop machine learning models to predict cognitive trajectories in participants with early Alzheimer's disease and presymptomatic individuals over 24 and 48 months respectively. DESIGN: Prognostic machine learning models were trained from a combination of demographics, cognitive tests, APOE genotype, and brain imaging data. SETTING: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), National Alzheimer's Coordinating Center (NACC), Open Access Series of Imaging Studies (OASIS-3), PharmaCog, and a Phase 3 clinical trial in early Alzheimer's disease were used for this study. PARTICIPANTS: A total of 2098 participants who had demographics, cognitive tests, APOE genotype, and brain imaging data, as well as follow-up visits for 24-48 months were included. MEASUREMENTS: Baseline magnetic resonance imaging, cognitive tests, demographics, and APOE genotype were used to separate decliners, defined as individuals whose CDR-Sum of Boxes scores increased during a predefined time window, from stable individuals. A prognostic model to predict decline at 24 months in early Alzheimer's disease was trained on 1151 individuals who had baseline diagnoses of mild cognitive impairment and Alzheimer's dementia from ADNI and NACC. This model was validated on 115 individuals from a placebo arm of a Phase 3 clinical trial and 76 individuals from the PharmaCog dataset. A second prognostic model to predict decline at 48 months in presymptomatic populations was trained on 628 individuals from ADNI and NACC who were cognitively unimpaired at baseline. This model was validated on 128 individuals from OASIS-3. RESULTS: The models achieved up to 79% area under the curve (cross-validated and out-of-sample). Power analyses showed that using prognostic models to recruit enriched cohorts of predicted decliners can reduce clinical trial sample sizes by as much as 51% while maintaining the same detection power. CONCLUSIONS: Prognostic tools for predicting cognitive decline and enriching clinical trials with participants at the highest risk of decline can improve trial quality, derisk endpoint failures, and accelerate therapeutic development in Alzheimer's disease.

Lipid nanoparticle formulations for optimal RNA-based topical delivery to murine airways.

INTRODUCTION: Lipid nanoparticles (LNP) have been successfully used as a platform technology for delivering nucleic acids to the liver. To broaden the application of LNPs in targeting non-hepatic tissues, we developed LNP-based RNA therapies (siRNA or mRNA) for the respiratory tract. Such optimized LNP systems could offer an early treatment strategy for viral respiratory tract infections such as COVID-19. METHODS: We generated a small library of six LNP formulations with varying helper lipid compositions and characterized their hydrodynamic diameter, size distribution and cargo entrapment properties. Next, we screened these LNP formulations for particle uptake and evaluated their potential for transfecting mRNA encoding green fluorescence protein (GFP) or SARS-CoV2 nucleocapsid-GFP fusion reporter gene in a human airway epithelial cell line in vitro. Following LNP-siGFP delivery, GFP protein knockdown efficiency was assessed by flow cytometry to determine %GFP+ cells and median fluorescence intensity (MFI) for GFP. Finally, lead LNP candidates were validated in Friend leukemia virus B (FVB) male mice via intranasal delivery of an mRNA encoding luciferase, using in vivo bioluminescence imaging. RESULTS: Dynamic light scattering revealed that all LNP formulations contained particles with an average diameter of <100 nm and a polydispersity index of <0.2. Human airway epithelial cell lines in culture internalized LNPs with differential GFP transfection efficiencies (73-97%). The lead formulation LNP6 entrapping GFP or Nuc-GFP mRNA demonstrated the highest transfection efficiency (97%). Administration of LNP-GFP siRNA resulted in a significant reduction of GFP protein expression. For in vivo studies, intranasal delivery of LNPs containing helper lipids (DSPC, DOPC, ESM or DOPS) with luciferase mRNA showed significant increase in luminescence expression in nasal cavity and lungs by at least 10 times above baseline control. CONCLUSION: LNP formulations enable the delivery of RNA payloads into human airway epithelial cells, and in the murine respiratory system; they can be delivered to nasal mucosa and lower respiratory tract via intranasal delivery. The composition of helper lipids in LNPs crucially modulates transfection efficiencies in airway epithelia, highlighting their importance in effective delivery of therapeutic products for airways diseases.

Imaging of the thorax after percutaneous thermal ablation of lung malignancies.

Image-guided thermal ablation is a minimally invasive treatment option for patients with early stage non-small cell lung cancer or metastatic disease to the lungs. Percutaneous ablation treats malignant tumours in situ, which precludes histopathological evaluation of the ablated tumours. Imaging studies are used as surrogates to assess technical and clinical success. Although it is not universally accepted, a common protocol for surveillance imaging includes contrast-enhanced computed tomography (CT) at 1, 3, 6, 9, 12, 18, 24 months, and yearly thereafter. Integrated 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (PET)/CT imaging is recommended at 3 and 12 months and when recurrent disease is suspected. There is a complex evolution of the ablation zone on CT and PET imaging studies. The zone of ablation, initially larger than the ablated tumour, undergoes gradual involution. In the process, it may cavitate and resemble a lung abscess. Different contrast-enhancement and radionuclide uptake patterns in and around the ablation zone may indicate a wide range of diagnostic possibilities from a normal physiological response to local progression. Ultimately, the zone of ablation may be replaced by a variety of findings including linear bands of density, pleural thickening, or residual necrotic tumour. Diagnostic and interventional radiologists interpreting post-ablation imaging studies must have a clear understanding of the ablation process and imaging findings on surveillance studies. Accurate and timely recognition of complications and/or local recurrence is necessary to guide further therapy. The purpose of this article is to review imaging protocols and salient imaging findings after thermal ablation of lung malignancies.

Long-term Survival Outcomes of 'Low Risk' Ductal Carcinoma in situ from a Territory-wide Cancer Registry.

AIMS: The LORIS trial is an ongoing phase III clinical trial on low risk ductal carcinoma in situ (DCIS). DCIS patients aged ≥46 years with screen-detected low/intermediate nuclear grade were considered low risk and were randomised into surveillance or standard surgery. Here we review the 10-year territory-wide breast cancer registry database and evaluate the clinical outcomes of low versus high risk DCIS patients. MATERIALS AND METHODS: This was a retrospective study of a prospectively maintained territory-wide breast cancer registry in Hong Kong. RESULTS: Between 1997 and 2006, 1391 DCIS patients were identified from the Hong Kong cancer registry breast cancer database. The mean age at diagnosis was 49.2 years (range 30-70). In total, 372 patients were classified as 'low risk', whereas the remaining 777 patients were classified as 'high risk'. After a median follow-up of 11.6 years, the 10-year overall breast cancer-specific survival of the entire DCIS cohort was 1136/1149 (98.9%). Overall breast cancer-specific survival of low risk DCIS was 99.5%, whereas that in high risk DCIS was 98.6% (Log-rank test, P = 0.208). Forty-six (12.4%) patients in the LORIS low risk group did not receive surgery, whereas 93 (12%) patients in the LORIS high risk group did not receive surgery. The 10-year breast cancer-specific survival in the non-operated low risk DCIS group was 97.8%; that in the non-operated high risk DCIS group was 96.7% (P = 1). CONCLUSION: Long-term survival of DCIS was excellent, especially in low risk DCIS, regardless of surgical treatment.

Image-guided biopsy in the age of personalised medicine: strategies for success and safety.

Oncology has progressed into an era of personalised medicine, whereby the therapeutic regimen is tailored to the molecular profile of the patient's cancer. Determining personalised therapeutic options is achieved by using tumour genomics and proteomics to identify the specific molecular targets against which candidate drugs can interact. Several dozen targeted drugs, many for multiple cancer types are already widely in clinical use. Molecular profiling of tumours is contingent on high-quality biopsy specimens and the most common method of tissue sampling is image-guided biopsy. Thus, for radiologists performing these biopsies, the paradigm has now shifted away from obtaining specimens simply for histopathological diagnosis to acquiring larger amounts of viable tumour cells for DNA, RNA, or protein analysis. These developments have highlighted the central role now played by radiologists in the delivery of personalised cancer care. This review describes the principles of molecular profiling assays and biopsy techniques for optimising yield, and describes a scoring system to assist in patient selection for percutaneous biopsy.

The value of interventional radiology in clinical trial teams: experience from the BATTLE lung cancer trials.

AIM: To report on the multidisciplinary approach, focusing specifically on the role of the interventional radiologist (IR), used to support the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) and BATTLE-2 trials. MATERIALS AND METHODS: Patients who underwent percutaneous image-guided biopsy for the BATTLE and BATTLE-2 trials were reviewed. A radiology-based, three-point, lesion-scoring system was developed and used by two IRs. Lesions were given a score of 3 (most likely to yield sufficient material for biomarker analysis) if they met the following criteria: size >2 cm, solid mass, demonstrated imaging evidence of viability, and were technically easy to sample. Lesions not meeting all four criteria were scored 2 with the missing criteria noted as negative factors. Lesions considered to have risks that outweighed potential benefits receive a score of 1 and were not biopsied. Univariate and multivariate analyses were performed to evaluate the score's ability to predict successful yield for biomarker adequacy. RESULTS: A total of 555 biopsies were performed. The overall yield for analysis of the required biomarkers was 86.1% (478/555), and 84% (268/319) and 88.9% (210/236) for BATTLE and BATTLE-2, respectively (p=0.09). Lesions receiving a score of 3 were adequate for biomarker analysis in 89% of cases. Lesions receiving a score of 2 with more than two negative factors were adequate for molecular analysis in 69.2% (IR1, p=0.03) and 74% (IR2, p=0.04) of cases. The two IRs scored 78.4% of the lesions the same indicating moderate agreement (kappa=0.55; 95% confidence interval [CI]: 0.48, 0.61). CONCLUSIONS: IRs add value to clinical trial teams by optimising lesions selected for biopsy and biomarker analysis.

Clinical outcomes of patients with ductal carcinoma in situ in Hong Kong: 10-year territory-wide cancer registry study.

BACKGROUND: Incidence of ductal carcinoma in situ (DCIS) has increased in recent decades because of breast cancer screening. This study comprised a long-term survival analysis of DCIS using 10-year territory-wide data from the Hong Kong Cancer Registry. METHODS: This study included all patients diagnosed with DCIS in Hong Kong from 1997 to 2006. Exclusion criteria were age <30 years or ≥70 years, lobular carcinoma in situ, Paget's disease, and co-existing invasive carcinoma. Patients were stratified into those diagnosed from 1997 to 2001 and those diagnosed from 2002 to 2006. The 5- and 10-year breast cancer-specific survival rates were evaluated; standardised mortality ratios were calculated. RESULTS: Among the 1391 patients in this study, 449 were diagnosed from 1997 to 2001, and 942 were diagnosed from 2002 to 2006. The mean age at diagnosis was 49.2±9.2 years. Overall, 51.2% of patients underwent mastectomy and 29.5% received adjuvant radiotherapy. The median follow-up interval was 11.6 years; overall breast cancer-specific mortality rates were 0.3% and 0.9% after 5 and 10 years of follow-up, respectively. In total, 109 patients (7.8%) developed invasive breast cancer after a considerable delay. Invasive breast cancer rates were comparable between patients diagnosed from 1997 to 2001 (n=37, 8.2%) and those diagnosed from 2002 to 2006 (n=72, 7.6%). CONCLUSION: Despite excellent long-term survival among patients with DCIS, these patients were more likely to die of breast cancer, compared with the general population of women in Hong Kong.

Stressful life events, gender and obesity: A prospective, population-based study of adolescents in British Columbia.

OBJECTIVE: To determine whether stressful life events are related to levels of obesity in a group of ethnically diverse Canadian youth and the extent to which the relationship differs by gender. METHODS: This study of 905 adolescents (age 13-17 years) from a BC population-based cohort (BASUS) used self-reported data from Wave 5 (2011 fall) on stressful life events and socio-demographic factors and from Wave 6 (2012 spring) on weight and height. Multivariable logistic regression models conditioned on known confounders and used a cross-product term for effect modification by gender. Post-estimation analysis calculated gender-specific predicted mean probabilities of having obesity associated with greater frequency of stressful life events. RESULTS: Compared to young men reporting no stressful life events in the previous year, young men reporting one event were nearly 50% more likely to have obesity at 6-month follow-up (OR 1.47 [95% CI: 0.63, 3.41]) and those reporting multiple stressful life events were twice as likely to have obesity at 6-month follow-up (OR 2.07 [95% CI: 0.79-5.43]). Only young women reporting multiple events showed a higher likelihood of having obesity at the end of the study (OR 1.32 [95% CI: 0.41-4.18]) than their counterparts reporting no life events. CONCLUSIONS: Results suggest that the frequency of major life events may be an important social stressor associated with obesity in adolescents, particularly for young men. However, findings should be replicated in larger samples using measured anthropometry to inform future obesity prevention strategies.

Hedgehog signaling in the airway epithelium of patients with chronic obstructive pulmonary disease.

Genome-wide association studies have linked gene variants of the receptor patched homolog 1 (PTCH1) with chronic obstructive pulmonary disease (COPD). However, its biological role in the disease is unclear. Our objective was to determine the expression pattern and biological role of PTCH1 in the lungs of patients with COPD. Airway epithelial-specific PTCH1 protein expression and epithelial morphology were assessed in lung tissues of control and COPD patients. PTCH1 mRNA expression was measured in bronchial epithelial cells obtained from individuals with and without COPD. The effects of PTCH1 siRNA knockdown on epithelial repair and mucous expression were evaluated using human epithelial cell lines. Ptch1+/- mice were used to assess the effect of decreased PTCH1 on mucous expression and airway epithelial phenotypes. Airway epithelial-specific PTCH1 protein expression was significantly increased in subjects with COPD compared to controls, and its expression was associated with total airway epithelial cell count and thickness. PTCH1 knockdown attenuated wound closure and mucous expression in airway epithelial cell lines. Ptch1+/- mice had reduced mucous expression compared to wildtype mice following mucous induction. PTCH1 protein is up-regulated in COPD airway epithelium and may upregulate mucous expression. PTCH1 provides a novel target to reduce chronic bronchitis in COPD patients.

Budget impact and cost-effectiveness analyses of direct-acting antivirals for chronic hepatitis C virus infection in Hong Kong.

The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171 per course while improving the rate of sustained virologic response (SVR) from 59-66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments ranged from $9724 to $29,189 per treatment success, which were all below the cost-effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection management over 5 years. A 50% change in DAA medication costs reflected a change in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs to the public hospital formulary yields a considerable budget increase but is still economically favorable to the local government.

The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.

Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in MinApc+/- mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks+Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.

Clinicopathological features of thyroid cancer in the elderly compared to younger counterparts: single-center experience.

PURPOSE: The incidence of thyroid cancer is increased in elderly patients. It tends to be larger and have more aggressive characteristics in these patients. Our aim was to compare features of thyroid carcinoma in geriatric and non-geriatric patients. METHODS: In total, 933 patients with thyroid cancer were retrospectively reviewed. Thyroid functions, ultrasonography features of malignant nodules, cytological and histopathological findings and the rates of recurrence and persistence were compared in patients ≥65 and <65 years old. RESULTS: There were 153 malignant foci in 109 (11.7%) patients ≥65 and 1185 malignant foci in 824 (88.3%) patients <65 years old. Mean nodule diameter was significantly higher in geriatric patients (p = 0.008). Most of the ultrasonographical features of malignant nodules were similar in two groups. Hypoechoic halo was observed in 16.4 and 28.6% of malignant nodules in geriatric and non-geriatric group, respectively (p = 0.034). There was no significant difference in cytological diagnosis. Histopathologically, tumor diameter, rates of microcarcinomas and incidentality were similar. Of all cancer types, 88.8% in geriatric and 93.9% in non-geriatric group were papillary thyroid cancer (p = 0.028). Hurthle cell cancer constituted 3.9 and 1.1% of carcinomas in geriatric and non-geriatric patients, respectively (p = 0.015); 2.0 and 0.2% of tumors in geriatric and non-geriatric group were anaplastic, respectively (p = 0.012). Capsular and vascular invasion, extrathyroidal extension, persistence and recurrence rates were similar. CONCLUSIONS: Rates of anaplastic cancer and Hurthle cell cancer which is known to have worser prognosis among other differentiated thyroid cancers are increased in geriatric ages. Cytological evaluation of thyroid nodules should strongly be considered due to increased tendency for aggressive tumor types in these patients.

Postpartum osteoporosis and vertebral fractures in two patients treated with enoxaparin during pregnancy.

Postpartum osteoporosis (PPO) is a rare disease associated with pregnancy and lactation period. Here, we report severe PPO and multiple vertebral compression fractures in two patients treated with enoxaparin--low-molecular-weight heparin (LMWH)--throughout their pregnancy. A 34-year-old woman who has delivered her second baby 3 months ago presented with severe low-back pain. She was treated with enoxaparin 40 mg/day for 8 months during her pregnancy. Dual-energy X-ray absorptiometry (DEXA) showed low T- and Z-scores in lumbar (L) vertebras. In magnetic resonance imaging (MRI), severe height losses in thoracic (T) 12, L1, and L2 vertebras were detected. She was diagnosed to have severe PPO and multiple vertebral compression fractures and was prescribed risedronate 35 mg/week, calcium, and vitamin D. The other patient was a 36-year-old woman diagnosed with PPO and vertebral fractures at the third week postpartum. She was also treated with enoxaparin 60 mg/day during her pregnancy. Severe osteoporosis in L vertebras and height losses indicative for compression fractures in T5-8, T11-12, and L2-5 vertebras were detected by DEXA and MRI, respectively. She was treated with calcitonin 200 U/day, calcium, and vitamin D. These findings suggest that vertebral compression fractures and PPO may be one of the causes of severe back pain in postpartum patients. Treatment with LMWH during pregnancy might be considered as a new risk factor for this rare condition.

Informing mental health policies and services in the EMR:cost-effective deployment of human resources to deliver integrated community-based care

For EMR countries to deliver the expectations of the Global Mental Health Action Plan 2013-2020 and the ongoing move towards universal health coverage, all health and social care providers need to innovate and transform their services to provide evidence-based health care that is accessible, cost-effective and with the best patient outcomes. For the primary and community workforce, this includes general medical practitioners, practice and community nurses, community social workers, housing officers, lay health workers, nongovernmental organizations and civil society, including community spiritual leaders/healers. This paper brings together the current best evidence to support transformation and discusses key approaches to achieve this, including skill mix and/or task shifting and integrated care. The important factors that need to be in place to support skill mix/task shifting and good integrated care are outlined with reference to EMR countries

Pour que les pays de la Région de la Méditerranée orientale puissent répondre aux attentes créées par le Plan d'action mondial sur la santé mentale 2013-2020 et pour faciliter le mouvement continu vers la couverture sanitaire universelle, tous les acteurs de la prestation de soins socio-sanitaires doivent faire preuve d'innovation et transformer leurs services afin de fournir des soins de santé fondés sur des bases factuelles qui soient accessibles, d'un bon rapport coût-efficacité et procurent les meilleurs résultats pour les patients. Pour ce qui est des personnels aux niveaux primaires et communautaires, ceci concerne les médecins généralistes, les infirmières praticiennes, les infirmières communautaires, les travailleurs sociaux communautaires, les responsables des logements sociaux,les travailleurs de la santé non professionnels, les membres des organisations non gouvernementales et de la société civile, y compris les leaders et les guérisseurs spirituels communautaires.Le présent article rassemble les meilleures bases factuelles actuellement disponibles à l'appui de cette transformation et examine les approches principales à cet égard, y compris l'éventail des compétences et/ou la délégation des tâches et les soins intégrés.Les facteurs importants qui doivent être en place à l'appui de l'éventail des compétences/la délégation des tâches et de bons soins intégrés sont présentés dans le contexte des pays de la Région de la Méditerranée orientale