Regional planning for meaningful person-centred care in mental health: context is the signal not the noise.

Person-centred care is at the core of a value-based health system. Its transformative potential is to enable and support key policy, planning and service developments across the system even when these go against the self-interest of individual major players. It offers a potent test for decision makers at all levels. It demands responses that are multi-level, empirically grounded, expert-informed and data-driven that must converge on the singularity of individuals in the places that they live. This requires different approaches that recognise, respect and reconcile two necessary but constitutionally disparate perspectives: the bureaucratic, overtly decontextualised, top-down, policy and planning objectives of central governments and the formally complex, dynamic and contextualised experience of individuals in the system. Conflating the latter with the former can lead unwittingly to a pervasive and reductive form of quasi-Taylorism that nearly always creates waste at the expense of value. This has parallel application in the treatment domain where outcomes are non-randomly clustered and partitioned by socioeconomic status, amplifying unwarranted variation by place that is striking in its magnitude and heterogeneity. In this paper, we propose that a combination of (1) relevant, local and sophisticated data planning, collection and analysis systems, (2) more detailed person-centred service planning and delivery and (3) system accountability through co-design and transparent public reporting of health system performance in a manner that is understandable, relevant, and locally applicable are all essential in ensuring planned and provided care is most appropriate to more than merely the 'average' person for whom the current system is built. We argue that only through a greater appreciation of healthcare as a complex adaptive (eco)system, where context is everything, and then utilising planning, analysis and management methodologies that reflect this reality is the way to achieve genuine person-centred care.

Anosognosia Is Associated With Greater Caregiver Burden and Poorer Executive Function in Huntington Disease.

BACKGROUND: Anosognosia, or unawareness of one's deficits, is estimated to occur in 25% to 50% of Huntington disease (HD). The relationship between anosognosia and increased caregiver burden found in other dementias has not been determined in HD. METHODS: Patient-caregiver dyads presenting to a statewide HD clinic were assessed using the Anosognosia Scale and grouped into "anosognosia" and "no anosognosia." Caregiver burden, measured by Zarit Burden Interview (ZBI) and Caregiver Burden Inventory (CBI), demographic data, and Unified Huntington's Disease Rating Scale, including Mini-Mental State Examination, Stroop, Trail Making, Verbal Fluency, and Symbol Digit Modalities Tests, were compared between groups. RESULTS: Of the 38 patients recruited, 10 (26.3%) met criteria for anosognosia. Patients with anosognosia elicited higher caregiver burden ratings on both the ZBI (mean difference 16.4 [12.1], P < .001) and CBI (16.7 [15.0], P < .005) while also demonstrating poorer executive function. Except for CAG burden score, between-group characteristics did not differ significantly. Stroop Interference predicted both anosognosia and caregiver burden. CONCLUSIONS: In HD, anosognosia is associated with greater caregiver burden and executive deficits. Its occurrence should prompt further patient assessment and increased caregiver support.

[Long-term experiences with corneal crosslinking in patients with progressive keratoconus at the University Eye Hospital in Tübingen, Germany]. / Langzeiterfahrungen des kornealen Crosslinkings bei Patienten mit progredientem Keratokonus an der Universitäts-Augenklinik Tübingen.

BACKGROUND AND PURPOSE: The corneal collagen crosslinking procedure has been clinically performed worldwide for approximately 20 years. The aim of the study was to analyze the long-term outcomes of corneal crosslinking at the University Eye Hospital in Tübingen. METHODS: In this retrospective study 136 consecutive eyes with progressive keratoconus from 107 patients were included. The observational period was from December 2008 to March 2018. The parameters analyzed were best corrected visual acuity (BCVA) and the keratometry values from elevation maps measured using a Scheimpflug camera. RESULTS: The study population of 107 patients included 96 (90%) male and 11 (10%) female subjects and the mean age was 23 ± 8 years. The mean observation time between corneal collagen crosslinking and the last follow-up examination was 42 ± 29 months. The mean postoperative BCVA showed a significant improvement from baseline at each point of postoperative measurement. The mean astigmatism and the mean Kmax showed a statistically significant reduction in the first 6 postoperative months. The mean thinnest point of the cornea showed a significant reduction in the first 6 months, after which the cornea thickness stabilized. No serious adverse events relating to the treatment were registered. CONCLUSION: Long-term outcomes after corneal collagen crosslinking showed a significant reduction of the keratometry values and the BCVA was significantly higher compared to the preoperative value at all times of observation. In conclusion, corneal collagen crosslinking was shown to be an effective and safe treatment for progressive keratoconus.

Risk factors for and management of anterior chamber intravitreal dexamethasone implant migration.

BACKGROUND: This study aimed to investigate the incidence of and risk factors for the anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®). METHODS: A retrospective review of 640 consecutive intravitreal dexamethasone implant injections was conducted from February 2011 through February 2018 at the University Eye Hospital in Tübingen, Germany. Those patients who experienced anterior chamber dexamethasone implant migrations were identified, as well as the reasons for the anterior chamber migration. The surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all of the eyes. Cross-tabulations, chi-squared tests, and Fisher's exact tests were used to assess the influences of different factors on the anterior chamber implant migrations. RESULTS: Overall, 4 eyes of four patients (0.63%) showed anterior chamber implant migrations. All four of the eyes were pseudophakic, and they had undergone prior vitrectomies. Three eyes had sclerally-fixated intraocular lenses, and one eye had a posterior chamber intraocular lens in the capsular bag, with a capsular tension ring due to partial zonular dehiscence. When comparing the vitrectomized eyes with reduced zonular/capsular bag complex integrity to the vitrectomized pseudophakic eyes with intact zonular/capsular bags, the former were significantly associated with an increased risk of anterior chamber implant migration (P = 0.008). The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber implant migration (P = 0.009). CONCLUSIONS: The anterior chamber migration of an intravitreal dexamethasone implant is a serious complication. To minimize the risk of permanent corneal edema, immediate removal of the implant with a 20-gauge alligator forceps over a 2.75-mm long clear corneal tunnel is important. Those patients with insufficient zonular support, defects, or missing posterior capsular membranes and vitrectomy histories present a high risk of anterior chamber dexamethasone implant migration.

Challenges for African swine fever vaccine development-" perhaps the end of the beginning."

African swine fever (ASF), an acute, viral hemorrhagic disease in domestic swine with mortality rates approaching 100%, is arguably the most significant emerging disease threat for the swine industry worldwide. Devastating ASF outbreaks and continuing epidemic in the Caucasus region and Russia (2007-to date) highlight significance of this disease threat. There is no vaccine for ASF, thus leaving animal slaughter the only effective disease control option. It is clear, however, that vaccination is possible since protection against reinfection with the homologous strain of African swine fever virus (ASFV) has been clearly demonstrated. Vaccine development has been hindered by large gaps in knowledge concerning ASFV infection and immunity, the extent of ASFV strain variation in nature and the identification of viral proteins (protective antigens) responsible for inducing protective immune responses in the pig. This review focuses on the challenges surrounding ASF vaccine design and development, with an emphasis on existing knowledge gaps.

African swine fever virus serotype-specific proteins are significant protective antigens for African swine fever.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available and progress is hindered by lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Available data from vaccination/challenge experiments in pigs indicate that ASF protective immunity may be haemadsorption inhibition (HAI) serotype-specific. Recently, we have shown that two ASFV proteins, CD2v (EP402R) and C-type lectin (EP153R), are necessary and sufficient for mediating HAI serological specificity (Malogolovkin et al., 2015).. Here, using ASFV inter-serotypic chimeric viruses and vaccination/challenge experiments in pigs, we demonstrate that serotype-specific CD2v and/or C-type lectin proteins are important for protection against homologous ASFV infection. Thus, these viral proteins represent significant protective antigens for ASFV that should be targeted in future vaccine design and development. Additionally, these data support the concept of HAI serotype-specific protective immunity.

Factors that influence the suitability of human organ-cultured corneas.

PURPOSE: The purpose was to assess the influence of donor and storage factors on the suitability of organ-cultured corneas for transplantation. METHODS: Data from 1340 donor corneas stored between 2009 and 2015 were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the suitability of grafts for transplantation. RESULTS: Forty-one percent (553/1340) of corneas were discarded. The leading causes were medical contraindication (20.2 %) and poor endothelial quality (19.3 %). Donor age influenced suitability for transplantation significantly. Corneas from donors aged 80 years and older were more likely to be discarded because of endothelial insufficiency (P < 0.0001). The cause of donor death including infection and multiple organ dsyfunction syndrom (MODS) increased the risk of bacterial or fungal contamination during organ culture (P = 0.007 and P = 0.014, respectively). Prolonged time between death and enucleation was associated with an increased risk of unsuitability for transplantation (P < 0.0001). The amount of time between death and corneoscleral disc excision and duration of storage influenced the suitability for transplantation (P = 0.0007 and P < 0.0001, respectively). CONCLUSION: Donor age, cause of death, storage time, death to enucleation and death to disc excision times influenced transplantation suitability. The percentage of discarded corneas may be reduced by shortening storage time, death to enucleation, and death to corneoscleral disc excision times. Setting a maximum donor age could reduce the percentage of discarded corneas. However, as long as there is a lack of donor corneas, we do not recommend any donor age limit.

Disrupted seasonal biology impacts health, food security and ecosystems.

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.

Causes that influence the detachment rate after Descemet membrane endothelial keratoplasty.

PURPOSE: To investigate Descemet graft (DG) detachment rate after Descemet membrane endothelial keratoplasty (DMEK) in relation to DG position. METHODS: A total of 175 consecutive pseudophakic eyes that underwent DMEK (175 eyes for Fuchs endothelial dystrophy) from September 2009 through February 2014 at the Tübingen Eye Hospital DG position were studied retrospectively by surgical video at the end of an operation. A group of 45 eyes showed a decentration of the DG with a stromal gap of ≥1.5 mm over at least 3 clock hours between the descematorhexis edge and the DG. DG detachment was documented at a mean follow-up of 13.9 ± 3.7 months after surgery. DG detachment was defined as a detachment of 20 % or more of the DG surface area. Various donor characteristics and patient characteristics were analyzed. RESULTS: The best spectacle-corrected visual acuity (BCVA) in the group of eyes with central well-positioned DG differed significantly from those of eyes with decentered DG. The preoperative BCVA in the central well-positioned DG group was 0.63 ± 0.40 logMAR, and in the decentered DG group 0.91 ± 0.51 logMAR (P < 0.001). The postoperative BCVA in the group of eyes with central well-positioned DG was 0.12 ± 0.11 logMAR, and in the group with decentered DG 0.23 ± 0.29 logMAR (P < 0.001). Endothelial cell density and patient characteristics such as age, gender, and intraocular pressure did not differ significantly between the two groups. The group of eyes with central well-positioned DG showed DG detachment in 12 %; the group with decentered DG findings had DG detachment in 87 % (P < 0.001) at the 12 month follow up. CONCLUSION: The present findings demonstrate the importance of central well-positioned DG and the relation of disease severity. Central well-positioned DG may reduce the incidence of DG detachment. Overlapping of the donor DG and the host Descemet membrane seems to be responsible for DG detachment. One possible way to enhance graft adhesion could be a larger descematorhexis, which avoids an overlapping. The second possible way could be not waiting too long for surgery to reduce disease severity.

African swine fever virus CD2v and C-type lectin gene loci mediate serological specificity.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available and progress is hindered by lack of knowledge concerning the extent of ASF virus (ASFV) strain diversity and the viral antigens responsible for protection in the pig. Available data from vaccination/challenge experiments in pigs indicate ASF protective immunity is haemadsorption inhibition (HAI) serotype-specific. A better understanding of ASFV HAI serological groups and their diversity in nature, as well as improved methods to serotype ASFV isolates, is needed. Here, we demonstrated that the genetic locus encoding ASFV CD2v and C-type lectin proteins mediates HAI serological specificity and that CD2v/C-type lectin genotyping provides a simple method to group ASFVs by serotype, thus facilitating study of ASFV strain diversity in nature, and providing information necessary for eventual vaccine design, development and efficacious use.

[Using intracameral cefuroxime reduces postoperative endophthalmitis rate: 5 years experience at the University Eye Hospital Tübingen]. / Reduktion der postoperativen Endophthalmitisrate durch intrakamerale Cerfuroximgabe: Ergebnisse aus 5 Jahren Erfahrungen an der Universitäts-Augenklinik Tübingen.

BACKGROUND: Cataract surgery is the most commonly performed surgical procedure in developed countries. The annual number of cataract surgeries in Germany is about 600,000. Acute postoperative endophthalmitis is a very severe and the most dreaded complication of cataract surgery. Various operative and non-operative measures have been suggested to prevent this serious complication. The European Society of Cataract & Refractive Surgeons (ESCRS) study of intracameral cefuroxime was the first prospective, randomised and partially placebo-controlled clinical trial showing the efficacy of antibiotic prophylaxis to prevent endophthalmitis in 2007. The aim of this retrospective study is to investigate a possible reduction of intracameral cefuroxime to prevent postoperative endophthalmitis at the University Eye Hospital Tübingen. PATIENTS AND METHODS: During the period from January 2002 to August 2013, 2 time periods were determined based on the adoption of intracameral cefuroxime injections after cataract surgery. From January 2002 to May 2009 patients received at the end of cataract surgery a subconjunctival administration of 50 mg of mezlocillin and postoperative antibiotic eye drops (gentamicin) without intracameral injection. From June 2009 to August 2013, patients received an intracameral injection of cefuroxime while antibiotic drops (moxifloxacin) were used too. The rates of postoperative infectious endophthalmitis during these 2 periods were calculated. RESULTS: 31 cases of endophthalmitis occurred in 31,386 cataract surgeries. The overall cumulative incidence was 0.99 per 1000 patients. The incidence in the first period without intracameral cefuroxime injection was 1.38 (95 % confidence interval [CI]: 1.03-1.72) per 1000 patients and in the second period 0.44 (95 % CI: 0.34-0.54) per 1000 patients (p < 0.001). CONCLUSION: Intracameral injection of cefuroxime reduces the rate of postoperative infectious endophthalmitis in cataract surgery significantly.

Novel gammaherpesvirus functions encoded by bovine herpesvirus 6 (bovine lymphotropic virus).

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique 141 kbp L-DNA region predicted to encode 77 genes. BoHV-6 encoded, in variable genomic regions, a novel complement of genes relative to other characterized macaviruses, probably contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, BoHV-6 encoded the first herpesviral protein (Bov2.b2) similar to cellular ornithine decarboxylase, an enzyme that catalyses the first and rate-limiting step in the biosynthesis of polyamines. Bov2.b2 conceivably mediates a novel mechanism by which BoHV-6 promotes cell-cycle-dependent viral replication.

The influence of axial length on confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography size measurements: a pilot study.

PURPOSE: To investigate the influence of axial length on SD-OCT and cSLO size measurements from the Heidelberg Spectralis. METHODS: In this pilot study, eight emmetropic pseudophakic eyes with subretinal visual implant were selected. The axial length was measured in three short (<22.5 mm), three medium (22.51-25.50 mm) and two long (>25.52 mm) eyes. The known size of subretinal implant sensor field (2800 × 2800 µm) was measured on 15 images per eye with cSLO and SD-OCT. RESULTS: The mean axial length was 20.8 ± 0.8 mm in short eyes, 23.3 ± 0.4 mm in medium eyes, and 26.3 ± 0.5 mm in long eyes respectively. We found in short eyes, in medium eyes and in long eyes a mean value of sensor field size measurements from cSLO of 3327 ± 9 µm, 2800 ± 9 µm and 2589 ± 12 µm and from SD-OCT of 3328 ± 9 µm, 2800 ± 12 µm and 2585 ± 19 µm respectively. The size measurements decreased in SD-OCT and cSLO measurements with longer axial lengths significantly (p < 0.0001). CONCLUSION: The present findings demonstrate accuracy of the scaling in cSLO and SD-OCT measurements of the Heidelberg Spectralis for emmetropic medium eyes. The size measurements from SD-OCT to those from cSLO were approximately equal. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. Further studies with larger sample sizes are needed to confirm findings.

[Refractive changes after Descemet membrane endothelial keratoplasty]. / Refraktionsänderung nach der Descemet-Membran-Endothelkeratoplastik.

Penetrating keratoplasty has different refractive disadvantages in contrast to posterior lamellar keratoplasty. For example, a decentered corneal trephination and a tilted trephination or unevenly tightened corneal sutures can cause an uncontrolled high astigmatism as well as a refractive change. Also the postoperative refraction may change over time as a result of wound healing, suture loosening or suture removal. The aim of this retrospective study was to investigate a possible refractive change after Descemet membrane endothelial keratoplasty (DMEK). A total of 139 pseudophakic eyes from 125 patients with endothelial decompensation had undergone DMEK surgery at the Tübingen Eye Clinic. After a mean postoperative time of 13.15 ± 2.98 months after DMEK discreet mean changes in the spherical equivalent of + 0.37 ± 0.87 diopters and the cylinder to - 0.45 ± 0.57 diopters were observed. The mean central corneal thickness decreased from 670 ± 70 µm to 544 ± 55 µm. In conclusion after DMEK a discreet induced hyperopic refractive shift due to the reversal of stromal swelling was observed.

[Management of corneal endothelial decompensation with Descemet's membrane endothelial keratoplasty in a patient with Ahmed glaucoma valve implant]. / Behandlung einer Endotheldekompensation mit der Descemet-Membran-Endothelkeratoplastik bei einem Patienten mit Ahmed-Implantat.

BACKGROUND: Currently, the main causes for developing bullous keratopathy are from problems related to intraocular surgery, trauma, infection, Fuchs' endothelial dystrophy and chronically elevated intraocular pressure. In the 1990s penetrating keratoplasty was once considered the therapy of choice for treatment of bullous keratopathy but in recent years it has been replaced by posterior lamellar keratoplasty. The Descemet membrane endothelial keratoplasty (DMEK) procedure represents the final development of posterior lamellar keratoplasty. The question now arises whether DMEK can be used in patients with bullous keratopathy and Ahmed glaucoma valve implant. CASE REPORT: A 72-year-old man was referred to our hospital for further evaluation with the diagnosis of bullous keratopathy and pseudoexfoliative glaucoma. The bullous keratopathy was caused by a variety of previous operations as well as decompensation of intraocular pressure. This article describes the therapy of bullous keratopathy by DMEK with existing Ahmed glaucoma valve implant. After surgery the cornea became clear and the best-corrected visual acuity improved from hand movement to 0.2. The intraocular pressure remained normal (10-14 mmHg) without antiglaucoma medication and the endothelial cell count decreased only slightly over a follow-up of 13 months. No complications were encountered. CONCLUSIONS: The DMEK surgical procedure seems to be possible in patients with Ahmed glaucoma valve implant and endothelial decompensation. However, further studies with a larger number of patients should follow to validate the replacement of penetrating keratoplasty and other posterior lamellar procedures by DMEK.

[Clinical results after Descemet membrane endothelial keratoplasty]. / Klinische Ergebnisse nach Descemet-Membran-Endothelzelltransplantation.

BACKGROUND: Diseases of the endothelial cell layer represent a common indication for perforating keratoplasty. In recent years posterior lamellar keratoplasty techniques have undergone a revival. The latest and most promising advancement is the isolated transplantation of Descemet's membrane (DM) with the endothelial layer - also known as Descemet's membrane endothelial keratoplasty (DMEK). This study was conducted to evaluate the clinical results of our DMEK patients and to assess the perioperative management. PATIENTS AND METHODS: 70 patients (75 eyes) with endothelial cell decompensation (50 eyes with Fuchs endothelial dystrophy and 25 eyes with bullous keratopathy) had undergone DMEK surgery at the Tübingen Eye Clinic. Visual acuity, refractive error, intraocular pressure, slit lamp examination, pachymetry and endothelial cell density were considered and re-examined at intervals of 1, 2 and 4 weeks postoperatively with further 3 monthly follow-ups. RESULTS: The mean age of the 45 female and 25 male patients at time of surgery was 73 years (36 to 91 years). The mean follow-up period was 12.1 months. One patient received an autologous and 4 patients a triple procedure. The mean preoperative LogMAR visual acuity was 0.87 ± 0.41. After 1 week a LogMAR visual acuity of 0.82 ± 0.4 was observed (p = 0.544). At the final examination the LogMAR visual acuity was 0.32 ± 0.35 (p < 0.001, a highly significant result as compared to the preoperative value). The most common and important complication was the dislocation of the transplant which was seen in 23 eyes (31 %). The use of intracameral air pressurisation re-appositioned most transplants. Complications such as highly elevated intraocular pressure, epithelial inclusions or endophthalmitis were not noted in any patient. CONCLUSIONS: DMEK surgery lead to a significant visual rehabilitation in a majority of patients in a relatively short postoperative period. It may be considered as a gold standard to treat isolated endothelial diseases as has been implicated by other studies. Thus, the safety and efficiency of this new type of posterior lamellar keratoplasty technique has been confirmed.

[Precut technique for Descemet's membrane endothelial keratoplasty, preparation and storage in organ culture]. / Precut Verfahren für Descemet-Membran-Endothelzelltransplantation, Präparation und Aufbewahrung in Kultur.

BACKGROUND: The preparation of the Descemet's membrane (DM) with the endothelial cell layer may be performed directly prior to surgery or as a precut tissue procedure. The purpose of the current study was the evaluation of the preparation technique and the tissue culture of 10 days regarding potential endothelial cell loss. MATERIALS AND METHODS: Ten corneoscleral rims with an average age of 64.3 years were dissected to obtain 8.5 mm in diameter endothelial-DM complexes, which subsequently were organ cultured for 10 days. The endothelial cell density (ECD) was assessed during the cell culture period at days 1., 4., 7. and 10. In addition, time of preparation and transplant morphology were evaluated. RESULTS: The DM with the endothelial cell layer could successfully be dissected from all corneoscleral rims. The average preparation time was 8.3 min. The average ECD count was 2183 ± 77 cells/mm2 prior to, 2094 ± 110 cells/ mm2 at day 1, 2078 ± 134 cells/mm2 at day 4, 1977 ± 107 cells/mm2 at day 7 and 1898 ± 170 cells/mm2 at day 10 after preparation, respectively. Endothelial cell loss was 4.1 %, 4.8 %, 9.4 % and 13.1 % after preparation, respectively. None of the transplants exhibited large, centrally-located cell deficits. CONCLUSION: The isolated storage of DM with the endothelial layer, without any stromal remnants, showed gratifying results under storage conditions in organ culture with a moderate ECD decrease. Hence, the implementation of a precut DMEK is conceivable.