Control over Imidazoquinoline Immune Stimulation by pH-Degradable Poly(norbornene) Nanogels.

The reactivation of the innate immune system by toll-like receptor (TLR) agonists holds promise for anticancer immunotherapy. Severe side effects caused by unspecific and systemic activation of the immune system upon intravenous injection prevent the use of small-molecule TLR agonists for such purposes. However, a covalent attachment of small-molecule imidazoquinoline (IMDQ) TLR7/8 agonists to pH-degradable polymeric nanogels could be shown to drastically reduce the systemic inflammation but retain the activity to tumoral tissues and their draining lymph nodes. Here, we introduce the synthesis of poly(norbornene)-based, acid-degradable nanogels for the covalent ligation of IMDQs. While the intact nanogels trigger sufficient TLR7/8 receptor stimulation, their degraded version of soluble, IMDQ-conjugated poly(norbornene) chains hardly activates TLR7/8. This renders their clinical safety profile, as degradation products are obtained, which would not only circumvent nanoparticle accumulation in the body but also provide nonactive, polymer-bound IMDQ species. Their immunologically silent behavior guarantees both spatial and temporal control over immune activity and, thus, holds promise for improved clinical applications.

Using routine health information data for research in low- and middle-income countries: a systematic review.

BACKGROUND: Routine health information systems (RHISs) support resource allocation and management decisions at all levels of the health system, as well as strategy development and policy-making in many low- and middle-income countries (LMICs). Although RHIS data represent a rich source of information, such data are currently underused for research purposes, largely due to concerns over data quality. Given that substantial investments have been made in strengthening RHISs in LMICs in recent years, and that there is a growing demand for more real-time data from researchers, this systematic review builds upon the existing literature to summarize the extent to which RHIS data have been used in peer-reviewed research publications. METHODS: Using terms 'routine health information system', 'health information system', or 'health management information system' and a list of LMICs, four electronic peer-review literature databases were searched from inception to February 202,019: PubMed, Scopus, EMBASE, and EconLit. Articles were assessed for inclusion based on pre-determined eligibility criteria and study characteristics were extracted from included articles using a piloted data extraction form. RESULTS: We identified 132 studies that met our inclusion criteria, originating in 37 different countries. Overall, the majority of the studies identified were from Sub-Saharan Africa and were published within the last 5 years. Malaria and maternal health were the most commonly studied health conditions, although a number of other health conditions and health services were also explored. CONCLUSIONS: Our study identified an increasing use of RHIS data for research purposes, with many studies applying rigorous study designs and analytic methods to advance program evaluation, monitoring and assessing services, and epidemiological studies in LMICs. RHIS data represent an underused source of data and should be made more available and further embraced by the research community in LMIC health systems.

Therapeutic Implications of Human Umbilical Cord Mesenchymal Stromal Cells in Attenuating Influenza A(H5N1) Virus-Associated Acute Lung Injury.

Background: Highly pathogenic avian influenza viruses can cause severe forms of acute lung injury (ALI) in humans, where pulmonary flooding leads to respiratory failure. The therapeutic benefits of bone marrow mesenchymal stromal cells (MSCs) have been demonstrated in a model of ALI due to influenza A(H5N1) virus. However, clinical translation is impractical and limited by a decline in efficacy as the age of the donor increases. Umbilical cord MSCs (UC-MSCs) are easier to obtain by comparison, and their primitive source may offer more-potent therapeutic effects. Methods: Here we investigate the therapeutic efficacy of UC-MSCs on the mechanisms of pulmonary edema formation and alveolar fluid clearance and protein permeability of A(H5N1)-infected human alveolar epithelial cells. UC-MSCs were also tested in a mouse model of influenza ALI. Results: We found that UC-MSCs were effective in restoring impaired alveolar fluid clearance and protein permeability of A(H5N1)-infected human alveolar epithelial cells. UC-MSCs consistently outperformed bone marrow MSCs, partly because of greater growth factor secretion of angiopoietin 1 and hepatocyte growth factor. Conditioned UC-MSC medium and UC-MSC exosomes were also able to recapitulate these effects. However, UC-MSCs only slightly improved survival of A(H5N1)-infected mice. Conclusions: Our results suggest that UC-MSCs are effective in restoring alveolar fluid clearance and protein permeability in A(H5N1)-associated ALI and confer functional in addition to practical advantages over conventional bone marrow MSCs.

Trauma Exposure, Posttraumatic Stress Disorder Symptoms Trajectory, and Disability Level Among Hospitalized Injury Survivors in Kenya.

Potentially traumatic events (PTEs) have been consistently associated with posttraumatic stress disorder (PTSD). However, the extent of association and attribution to subsequent disability has varied, with limited studies conducted in urban low-income contexts. This longitudinal study estimated the trajectory of PTSD symptoms up to 7 months after hospitalization and the associated disability level among adult patients who had been hospitalized due to injury. Adult injury patients (N = 476) admitted to Kenyatta National Hospital in Nairobi, Kenya, were interviewed in person in the hospital, and via phone at 1, 2-3, and 4-7 months after hospital discharge. Using latent growth curve modeling, two trajectories of PTSD symptoms emerged: (a) persistently elevated PTSD symptoms (9.2%), and (b) low PTSD symptoms (90.8%). Number of PTEs experienced remained moderately associated with the elevated trajectory after controlling for in-hospital depressive symptoms. Having previously witnessed killings or serious injuries, AOR = 2.32, 95% CI [1.07, 5.05]; being female, AOR = 4.74, 95% CI [4.53, 4.96]; elevated depressive symptoms during hospitalization, AOR = 2.96, 95% CI [1.28, 6.83]; and having no household savings/assets, AOR = 1.28, 95% CI [1.13, 1.44], were associated with the elevated PTSD symptoms trajectory class after controlling for other risk factors. Latent membership in the elevated PTSD trajectory was associated with a significantly higher level of disability several months after hospital discharge, p < .001, after controlling for injury and demographic characteristics. These results underline the associations among in-hospital depressive symptoms, witnessing atrocities, and poverty, and an elevated PTSD symptoms trajectory.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Exposición al trauma, Trayectoria de los síntomas del trastorno de estrés postraumático y nivel de discapacidad entre los Sobrevivientes de lesiones hospitalizados en Kenia TRAYECTORIAS DE LOS SíNTOMAS DE TEPT EN SOBREVIVIENTES DE TRAUMAS DE KENIA Los eventos potencialmente traumáticos (EPT) se han asociado sistemáticamente con el trastorno de estrés postraumático (TEPT). Sin embargo, el grado de asociación y la atribución a la discapacidad posterior ha variado, con estudios limitados realizados en contextos urbanos de bajos ingresos. Este estudio longitudinal estimo la trayectoria de los síntomas de TEPT hasta 7 meses después de la hospitalización y el nivel de discapacidad asociado entre los pacientes adultos que habían sido hospitalizados debido a una lesión. Pacientes adultos con lesiones (n = 476) ingresados en el Hospital Nacional Kenyatta en Nairobi, Kenia, fueron entrevistados en persona en el hospital y por teléfono a 1, 2-3 y 4-7 meses después de que el hospital los dio de alta. Utilizando el modelo de curva de crecimiento latente, surgieron dos trayectorias de los síntomas de TEPT: síntomas de TEPT persistentemente elevados (9.2%) y (b) síntomas de TEPT bajos (90.8%). El número de las EPT experimentados permanecieron moderadamente asociados con la trayectoria elevada después de controlar los síntomas depresivos en el hospital. Haber previamente presenciado asesinatos o lesiones graves, AOR = 2,32; IC del 95% [1,07, 5,05]; ser mujer, AOR = 4.74, IC 95% [4.53, 4.96]; tener síntomas depresivos elevados durante la hospitalización, AOR = 2.96, IC 95% [1.28, 6.83]; y carencia de ahorros / activos de los hogares, AOR = 1.28, IC del 95% [1.13, 1.44], se asociaron con la clase de trayectoria de síntomas de trastorno de estrés postraumático elevados después de controlar otros factores de riesgo. La membresía latente en la trayectoria del trastorno de estrés postraumático elevada se asoció con un nivel de discapacidad significativamente mayor varios meses después del alta hospitalaria, p <.001, después de controlar por características de lesiones y demografía. Estos resultados subyacen a las asociaciones entre los síntomas depresivos intrahospitalarios, presenciar atrocidades y pobreza y una trayectoria de síntomas de TEPT elevada.

Reduction of operative mortality after implementation of Surgical Outcomes Monitoring and Improvement Programme by Hong Kong Hospital Authority.

INTRODUCTION: Since 2008, the Hong Kong Hospital Authority has implemented a Surgical Outcomes Monitoring and Improvement Programme (SOMIP) at 17 public hospitals with surgical departments. This study aimed to assess the change in operative mortality rate after implementation of SOMIP. METHODS: The SOMIP included all Hospital Authority patients undergoing major/ultra-major procedures in general surgery, urology, plastic surgery, and paediatric surgery. Patients undergoing liver or renal transplantation or who had multiple trauma or massive bowel ischaemia were excluded. In SOMIP, data retrieval from the Hospital Authority patient database was performed by six full-time nurse reviewers following a set of precise data definitions. A total of 230 variables were collected for each patient, on demographics, preoperative and operative variables, laboratory test results, and postoperative complications up to 30 days after surgery. In this study, we used SOMIP cumulative 5-year data to generate risk-adjusted 30-day mortality models by hierarchical logistic regression for both emergency and elective operations. The models expressed overall performance as an annual observed-to-expected mortality ratio. RESULTS: From 2009/2010 to 2015/2016, the overall crude mortality rate decreased from 10.8% to 5.6% for emergency procedures and from 0.9% to 0.4% for elective procedures. From 2011/2012 to 2015/2016, the risk-adjusted observed-to-expected mortality ratios showed a significant downward trend for both emergency and elective operations: from 1.126 to 0.796 and from 1.150 to 0.859, respectively (Mann- Kendall statistic = -0.8; P<0.05 for both). CONCLUSION: The Hospital Authority's overall crude mortality rates and risk-adjusted observed-to-expected mortality ratios for emergency and elective operations significantly declined after SOMIP was implemented.

Health-related behaviours and mental health in Hong Kong employees.

BACKGROUND: Poor physical and mental health in employees can result in a serious loss of productivity. Early detection and management of unhealthy behaviours and mental health symptoms can prevent productivity loss and foster healthy workplaces. AIMS: To examine health-related behaviours, mental health status and help-seeking patterns in employees, across different industries in Hong Kong. METHODS: Participants were telephone-interviewed and assessed using the Case-finding and Help Assessment Tool (CHAT) with employee lifestyle risk factors, mental health issues and help-seeking intentions screened across eight industries. Subsequent data analysis involved descriptive statistics and chi-square tests. RESULTS: There were 1031 participants. Key stressors were work (30%), family (19%), money (14%) and interpersonal issues (5%). Approximately 18, 9 and 9% of participants were smokers, drinkers and gamblers, respectively, and only 51% exercised regularly. Depressive and anxiety symptoms were reported by 24 and 31% of employees, respectively. Issues for which they wanted immediate help were interpersonal abuse (16%), anxiety (15%), anger control (14%) and depression (14%). Employees with higher educational attainment were less likely to smoke, drink and gamble than those with lower attainment. Lifestyle and mental health status were not associated with income. Employees in construction and hotel industries smoked more and those in manufacturing drank more than those in other industries. CONCLUSIONS: Physical and mental health of Hong Kong employees are concerning. Although employee assistance programmes are common among large companies, initiation of proactive engagement approaches, reaching out to those employees in need and unlikely to seek help for mental health issues, may be useful.

How well are we managing fragility hip fractures? A narrative report on the review with the attempt to setup a Fragility Fracture Registry in Hong Kong.

INTRODUCTION: In setting up a disease registry for fragility fractures in Hong Kong, we conducted a retrospective systematic study on the management of fragility hip fractures. Patient outcomes were compared with the standards from our orthopaedic working group and those from the British Orthopaedic Association that runs a mature fracture registry in the United Kingdom. METHODS: Clinical data on fragility hip fracture patients admitted to six acute major hospitals in Hong Kong in 2012 were captured. These included demographics, pre- and post-operative assessments, discharge details, complications, and 1-year follow-up information. Analysis was performed according to the local standards with reference to those from the British Orthopaedic Association. RESULTS: Overall, 91.0% of patients received orthopaedic care within 4 hours of admission and 60.5% received surgery within 48 hours. Preoperative geri-orthopaedic co-management was received by 3.5% of patients and was one of the reasons for the delayed surgery in 22% of patients. Only 22.9% were discharged with medication that would promote bone health. Institutionalisation on discharge significantly increased by 16.2% (P<0.001). Only 35.1% of patients attended out-patient follow-up 1 year following fracture, and mobility had deteriorated in 69.9% compared with the premorbid state. Death occurred in 17.3% of patients within a year of surgery compared with 1.6% mortality rate in a Hong Kong age-matched population. CONCLUSIONS: The efficiency and quality of acute care for fragility hip fracture patients was documented. Regular geri-orthopaedic co-management can enhance acute care. Much effort is needed to improve functional recovery, prescription of bone health medications, attendance for follow-up, and to decrease institutionalisation. A Fracture Liaison Service is vital to improve long-term care and prevent secondary fractures.

Efficacy and safety of hylan G-F 20 injection in treatment of knee osteoarthritis in Chinese patients: results of a prospective, multicentre, longitudinal study.

OBJECTIVE: To study the efficacy and safety of single intra-articular injection of 6-mL hylan G-F 20 in Chinese patients with symptomatic knee osteoarthritis. DESIGN: Prospective case series. SETTING: Six government hospitals in Hong Kong. PATIENTS: Patients with primary knee osteoarthritis were recruited from six government hospitals from 1 October 2010 to 31 May 2012. All patients received 6-mL intra-articular injection of hylan G-F 20. MAIN OUTCOME MEASURES: Pain visual analogue scale, functional visual analogue scale, and 5-point Likert scale on change of pain and function were assessed. Adverse events were checked. Radiographs were taken pre-injection and at 3 months and 1 year. RESULTS: A total of 110 knees of 95 patients with primary knee osteoarthritis were treated. The mean age of the patients was 62 (standard deviation, 9.8) years. All patients completed 1 year of follow-up. The mean pain visual analogue scale, functional visual analogue scale, and Likert value for pain and function showed statistically significant improvements at 6 weeks, 3 months, 6 months, and 1 year compared with the pre-injection values. No significant correlations were found between changes in visual analogue scale and age, body mass index, pre-injection radiological osteoarthritis severity, serum erythrocyte sedimentation rate, or C-reactive protein. Serial radiographs did not show any changes in the radiological severity of knee osteoarthritis. Overall, 16.4% of the patients experienced mild and self-limiting adverse events. CONCLUSION: Hylan G-F 20 is a safe and effective therapy to relieve pain and improve function for up to 1 year in Chinese patients with knee osteoarthritis.

Burden of itch in epidermolysis bullosa.

BACKGROUND: Itch is an unpleasant feeling that leads to scratching. It is a common, but understudied, problem in patients with epidermolysis bullosa (EB). OBJECTIVES: We measured the prevalence and characteristics of itch in the three major forms of EB: generalized EB simplex (EBS), junctional EB (JEB) and dystrophic EB (DEB). METHODS: Forty patients with EB were recruited from two tertiary care centres and one patient organization. The sample included 19 patients with EBS, seven with JEB and 14 with DEB. Patients completed the Leuven Itch Scale (LIS), a multidimensional self-report instrument that quantifies the frequency, duration, severity, distress, consequences and surface area of itch. This instrument has good clinimetric properties. RESULTS: Itch occurred in 85% of the patients, with substantial differences across the subtypes (EBS 74%, JEB 100%, DEB 93%). Itch, in all its dimensions, was most pronounced in patients with JEB and DEB, and less prominent in patients with EBS. The scores were significantly different for itch frequency, severity, distress and surface area, and the overall itch scores were comparable with those of atopic dermatitis. Itch mainly occurred in a hot environment (65%) and when sweating (62%). The most prevalent consequences were difficulty in falling asleep (88%) and lesions from scratching (85%). Differences between the three major subtypes were also observed in terms of circumstances, consequences and sensory characteristics. CONCLUSIONS: As expected, itch is common among patients with EB. All aspects of itch measured by the LIS were more severe in JEB and DEB than in EBS.

The needs of parents with children suffering from lethal epidermolysis bullosa.

BACKGROUND: Some subtypes of the heterogeneous genetic blistering disease epidermolysis bullosa (EB) lead to lethality in childhood. The severity and extent of blistering leaves these patients living in excruciating pain and distress their entire lives. Parents of these patients experience some specific problems, such as the unfamiliarity of EB amongst healthcare professionals and the suffering and loss of their child. OBJECTIVE: To identify the needs of parents who have lost their child to lethal EB. METHODS: A qualitative study was performed, comprising semistructured, in-depth interviews with 16 parents. The transcripts were analysed and common themes were identified. RESULTS: Parents indicated that they have the need (i) for a fast and correct referral to a specialized EB clinic, (ii) to be informed as honestly as possible about the diagnosis and lethal prognosis, (iii) to have a structured network of caregivers in the palliative care, (iv) to be involved in the care and the medical decisions involving their child, (v) to be informed about the end of life and to discuss euthanasia, (vi) for guidance and to have remembrances of their child, and (vii) for genetic counselling. CONCLUSIONS: Our job as healthcare professionals is to provide the best care not only for children suffering from lethal EB, but also for their parents. In this study, parents have provided us with some guidelines to care for them. However, it is important to keep in mind that every parent is different, and that the guidance should be tailored to their individual needs.

Long-term follow-up of patients with Herlitz-type junctional epidermolysis bullosa.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a rare, autosomal recessive disease caused by absence of the epidermal basement membrane adhesion protein laminin-332. It is characterized by extensive and devastating blistering of the skin and mucous membranes, leading to death in early childhood. OBJECTIVES: To present the results of the long-term follow-up of a cohort of patients with JEB-H, and to provide guidelines for prognosis, treatment and care. METHODS: All patients with JEB-H included in the Dutch Epidermolysis Bullosa (EB) Registry between 1988 and 2011 were followed longitudinally by our EB team. Diagnosis was established using immunofluorescence antigen mapping, electron microscopy and DNA analysis. RESULTS: In total, we included 22 patients with JEB-H over a 23-year period. Their average age at death was 5.8 months (range 0.5-32.6 months). The causes of death were, in order of frequency: failure to thrive, respiratory failure, pneumonia, dehydration, anaemia, sepsis and euthanasia. The pattern of initial weight gain was a predictor of lifespan in these patients. Invasive treatments to extend life did not promote survival in our patients. CONCLUSIONS: It is important to diagnose JEB-H as soon as possible after birth so that the management can be shifted from life-saving to comfort care. The palliative end-of-life care can take place in hospital, but is also safe in the home setting. Suffering in patients with JEB-H can become so unbearable that in some patients who do not respond to adequate analgesic and sedative treatment, newborn euthanasia, performed according to the Groningen protocol, is legally permitted in the Netherlands.

The ultraviolet photodissociation of CS2: the S(1D2) channel.

The photodissociation of CS(2) has been investigated using velocity-map ion imaging of the S((1)D(2)) atomic photofragments following excitation at 193 nm and at longer wavelengths close to the S((1)D(2)) channel threshold. The experiments probe regions both above and below the energetic barrier to linearity on the (1)Σ(u) (+)((1)B(2)) potential energy surface. The imaging data in both regions indicate that the electronic angular momentum of the S((1)D(2)) atom products is unpolarized, but also reveal different dissociation dynamics in the two regions. Excitation above the barrier to linearity yields an inverted CS((1)Σ(+)) vibrational population distribution, whereas the long-wavelength state-to-state results following excitation below the barrier reveal CS((1)Σ(+))(v, J) coproduct state distributions which are consistent with a statistical partitioning of the energy. Below the barrier, photofragment excitation spectra point to an enhancement of the singlet channel for K = 1, relative to K = 0, where K is the projection of the angular momentum along the principal axis, in agreement with previous work. However, the CS cofragment product state distributions are found to be insensitive to K. It is proposed that dissociation below the barrier to linearity occurs primarily on a surface with a significant potential energy well and without an exit channel barrier, such as that for the ground electronic state. However, oscillatory structure is also observed in the kinetic energy release distributions, which is shown to be consistent with a mapping of parent molecule bending motion. This could indicate the operation of competing direct and indirect dissociation mechanisms below the barrier to linearity.

Understanding the challenges associated with the use of data from routine health information systems in low- and middle-income countries: A systematic review.

BACKGROUND: Routine health information systems (RHISs) are crucial to informing decision-making at all levels of the health system. However, the use of RHIS data in low- and middle-income countries (LMICs) is limited due to concerns regarding quality, accuracy, timeliness, completeness and representativeness. OBJECTIVE: This study systematically reviewed technical, behavioural and organisational/environmental challenges that hinder the use of RHIS data in LMICs and strategies implemented to overcome these challenges. METHOD: Four electronic databases were searched for studies describing challenges associated with the use of RHIS data and/or strategies implemented to circumvent these challenges in LMICs. Identified articles were screened against inclusion and exclusion criteria by two independent reviewers. RESULTS: Sixty studies met the inclusion criteria and were included in this review, 55 of which described challenges in using RHIS data and 20 of which focused on strategies to address these challenges. Identified challenges and strategies were organised by their technical, behavioural and organisational/environmental determinants and by the core steps of the data process. Organisational/environmental challenges were the most commonly reported barriers to data use, while technical challenges were the most commonly addressed with strategies. CONCLUSION: Despite the known benefits of RHIS data for health system strengthening, numerous challenges continue to impede their use in practice. IMPLICATIONS: Additional research is needed to identify effective strategies for addressing the determinants of RHIS use, particularly given the disconnect identified between the type of challenge most commonly described in the literature and the type of challenge most commonly targeted for interventions.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

BACKGROUND: There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS: A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS: A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION: Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.

Junctional epidermolysis bullosa of late onset explained by mutations in COL17A1.

BACKGROUND: Junctional epidermolysis bullosa of late onset (JEB-lo) is a rare disease characterized by blistering of primarily the hands and feet starting in childhood. The pathogenesis remains unclear. OBJECTIVES: To clarify the pathogenesis of JEB-lo. METHODS: Two patients with JEB-lo, a brother and a sister, were examined using electron microscopy (EM), immunofluorescence (IF) antigen mapping and molecular analysis. RESULTS: We found subtle changes in IF antigen mapping and EM. The most remarkable changes were loss of the apical-lateral staining of monoclonal antibodies (mAbs) against type XVII collagen (Col17), and a broadened distribution of mAb staining against the ectodomain of Col17, laminin-332 and type VII collagen. Mutation analysis of COL17A1, encoding Col17, showed a compound heterozygosity for a novel mutation c.1992_1995delGGGT and the known mutation c.3908G>A in both patients. The deletion c.1992_1995delGGGT results in a premature termination codon and mRNA decay, leaving the patients functionally hemizygous for the missense mutation c.3908G>A (p.R1303Q) in the noncollagenous 4 domain of Col17. CONCLUSIONS: JEB-lo is an autosomal recessive disorder caused by mutations in COL17A1, and subtle aberrations in EM and IF antigen mapping are clues to diagnosis.

Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence and population carrier frequency in the Netherlands.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a lethal, autosomal recessive blistering disease caused by null mutations in the genes coding for the lamina lucida/densa adhesion protein laminin-332 (LAMB3, LAMA3 and LAMC2). OBJECTIVES: To present the diagnostic features and molecular analyses of all 22 patients with JEB-H in the Dutch Epidermolysis Bullosa Registry between 1988 and 2011, and to calculate the disease incidence and carrier frequency in the Netherlands. METHODS: All patients were analysed with immunofluorescence antigen mapping (IF), electron microscopy (EM) and molecular analysis. RESULTS: The mean lifespan of our patients with JEB-H was 5·8 months (range 0·5-32·6). IF showed absent (91%) or strongly reduced (9%) staining for laminin-332 with monoclonal antibody GB3. In EM the hemidesmosomes and sub-basal dense plates were hypoplastic or absent. We identified mutations in all 22 patients: in 19 we found LAMB3 mutations, in two LAMA3 mutations, and in one LAMC2 mutations. We found three novel splice site mutations in LAMB3: (i) c.29-2A>G resulting in an out-of-frame skip of exon 3 and a premature termination codon (PTC); (ii) c.1289-2_1296del10 leading to an out-of-frame skip of exon 12 and a PTC; and (iii) c.3228+1G>T leading to an exon 21 skip. CONCLUSIONS: All diagnostic tools should be evaluated to clarify the diagnosis of JEB-H. We have identified 11 different mutations in 22 patients with JEB-H, three of them novel. In the Netherlands the incidence rate of JEB-H is 4·0 per one million live births. The carrier frequency of a JEB-H mutation in the Dutch population is 1 in 249.

The first 5 years since trauma center designation in the Hong Kong Special Administrative Region, People's Republic of China.

BACKGROUND: In 1994, the Hong Kong Special Administrative Region (HKSAR) introduced plans to implement a trauma system based on the recommendations outlined by Professor Donald Trunkey in his report to the local Hospital Authority. Five government-subsidized public hospitals were subsequently designated as trauma centers in 2003. This article reviews the initial experience in these five centers. METHODS: Prospective trauma registries from January 2004 to December 2008 were reviewed. Primary clinical outcome measures were hospital mortality. The Trauma and Injury Severity Score methodology was used for benchmarking with the Major Trauma Outcome Study (MTOS) database. RESULTS: The majority (83.3%) of the 10,462 patients suffered from blunt trauma. Severe injury, defined as Injury Severity Score>15, occurred in 29.7% of patients. The leading causes of trauma were motor vehicle collisions and falls, with crude hospital mortality rates of 6.9% and 10.7%, respectively. The M-statistic was 0.95, indicating comparable case-mix with the MTOS. The worst outcome occurred in the first year. Significant improvement was seen in patients with penetrating injuries. By 2008, these patients had significantly higher survival rates than expected (Z-statistic=0.85). Although the overall mortality rates for blunt trauma were higher than expected, the difference was no longer statistically significant from the second year onward. CONCLUSIONS: The case-mix of trauma patients in the HKSAR is comparable with that of the MTOS. A young trauma system relatively unburdened by dissimilar reimbursement and patient access issues may achieve significant improvement and satisfactory patient outcomes. Our findings may serve as a useful benchmark for HK and other Southeast Asian cities and trauma systems to establish local coefficients for future evaluations.

Hypertrophic cardiomyopathy and exercise restrictions: time to let the shackles off?

The health benefits of physical activity are well documented. Patients with hypertrophic cardiomyopathy (HCM) are often discouraged from participating in physical activity due to a perceived increase in the risk of sudden cardiac death (SCD). As a result, only 45% of patients with HCM meet the minimum guidelines for physical activity, and many report an intentional reduction in exercise following diagnosis. Despite most SCD being unrelated to HCM, guidelines traditionally focused on the avoidance of potential risk through restriction of exercise, without clear recommendations on how to negate the negative health impact of inactivity. Retrospective reviews have demonstrated that the majority of cardiac arrests in patients with HCM occurred at rest or on mild exertion and that the overall incidence of HCM-related SCD is significantly lower than previously reported. We will discuss current international guidelines and recommendations and consider the outcomes of various studies that have investigated the effects of exercise of different intensities on patients with HCM. In light of the growing evidence suggesting that carefully guided exercise can be both beneficial and safe in patients with HCM, we ask whether it is time to let the shackles off exercise restriction in HCM.

Longitudinal depressive and anxiety symptoms of adult injury patients in Kenya and their risk factors.

Background: Injuries account for a significant proportion of the health and economic burden for populations in low- and middle-income countries. However, little is known about psychological distress trajectories amongst injury survivors in low- and middle-income countries.Methods: Adult injury patients (n = 644) admitted to Kenyatta National Hospital in Nairobi, Kenya, were enrolled and interviewed in the hospital, and at 1, 2-3, and 4-7 months after hospital discharge through phone to assess depressive and anxiety symptoms and level of disability. Growth mixture modeling was applied to identify latent trajectories of depressive and anxiety symptoms.Results: Elevated depressive and moderate-level anxiety symptoms (13%) and low depressive and anxiety symptoms (87%) trajectories were found between hospitalization and up to seven months after hospital discharge. Being female, prior trauma experience, longer hospitalization, worse self-rated health status while in the hospital, and lack of monetary assistance during hospitalization were associated with the elevated symptoms trajectory. The higher symptoms trajectory associated with higher disability levels after hospital discharge and significantly lower proportion of resuming daily activities and work.Conclusion: The persistence of elevated depressive symptoms and associated reduced functioning several months after physical injury underscores the importance of identifying populations at risk for preventive and early interventions.Implications for RehabilitationHealth providers following up with injury survivors should screen for depressive and anxiety symptomsSpecial attention to women and people with a potential traumatic exposure historyIncorporation of evidence-based culturally adapted psychosocial interventions in rehabilitation and outpatient clinics.