Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Large differences in the organization of palliative care in nursing homes in six European countries: findings from the PACE cross-sectional study.

BACKGROUND: To be able to provide high-quality palliative care, there need to be a number of organizational structures available in the nursing homes. It is unclear to what extent such structures are actually present in nursing homes in Europe. We aim to examine structural indicators for quality of palliative care in nursing homes in Europe and to evaluate the differences in terms of availability of and access to palliative care, infrastructure for residents and families, multidisciplinary meetings and quality improvement initiatives. METHODS: A PACE cross-sectional study (2015) of nursing homes in Belgium, England, Finland, Italy, the Netherlands and Poland. Nursing homes (N = 322) were selected in each country via proportional stratified random sampling. Nursing home administrators (N = 305) filled in structured questionnaires on nursing home characteristics. Organization of palliative care was measured using 13 of the previously defined IMPACT structural indicators for quality of palliative care covering four domains: availability of and access to palliative care, infrastructure for residents and families, multidisciplinary meetings and quality improvement initiatives. We calculated structural indicator scores for each country and computed differences in indicator scores between the six countries. Pearson's Chi-square test was used to compute the p-value of each difference. RESULTS: The availability of specialist palliative care teams in nursing homes was limited (6.1-48.7%). In Finland, Poland and Italy, specialist advice was also less often available (35.6-46.9%). Up to 49% of the nursing homes did not provide a dedicated contact person who maintained regular contact with the resident and relatives. The 24/7 availability of opioids for all nursing home residents was low in Poland (37.5%). CONCLUSIONS: This study found a large heterogeneity between countries in the organization of palliative care in nursing homes, although a common challenge is ensuring sufficient structural access to specialist palliative care services. Policymakers and health and palliative care organizations can use these structural indicators to identify areas for improvement in the organization of palliative care.

Consensus on treatment for residents in long-term care facilities: perspectives from relatives and care staff in the PACE cross-sectional study in 6 European countries.

BACKGROUND: In long-term care facilities often many care providers are involved, which could make it difficult to reach consensus in care. This may harm the relation between care providers and can complicate care. This study aimed to describe and compare in six European countries the degree of consensus among everyone involved in care decisions, from the perspective of relatives and care staff. Another aim was to assess which factors are associated with reporting that full consensus was reached, from the perspective of care staff and relatives. METHODS: In Belgium, England, Finland, Italy, the Netherlands and Poland a random sample of representative long-term care facilities reported all deaths of residents in the previous three months (n = 1707). This study included residents about whom care staff (n = 1284) and relatives (n = 790) indicated in questionnaires the degree of consensus among all involved in the decision or care process. To account for clustering on facility level, Generalized Estimating Equations were conducted to analyse the degree of consensus across countries and factors associated with full consensus. RESULTS: Relatives indicated full consensus in more than half of the residents in all countries (NL 57.9% - EN 68%), except in Finland (40.7%). Care staff reported full consensus in 59.5% of residents in Finland to 86.1% of residents in England. Relatives more likely reported full consensus when: the resident was more comfortable or talked about treatment preferences, a care provider explained what palliative care is, family-physician communication was well perceived, their relation to the resident was other than child (compared to spouse/partner) or if they lived in Poland or Belgium (compared to Finland). Care staff more often indicated full consensus when they rated a higher comfort level of the resident, or if they lived in Italy, the Netherland, Poland or England (compared to Finland). CONCLUSIONS: In most countries the frequency of full consensus among all involved in care decisions was relatively high. Across countries care staff indicated full consensus more often and no consensus less often than relatives. Advance care planning, comfort and good communication between relatives and care professionals could play a role in achieving full consensus.

Care staff's self-efficacy regarding end-of-life communication in the long-term care setting: Results of the PACE cross-sectional study in six European countries.

BACKGROUND: An important part of palliative care is discussing preferences at end of life, however such conversations may not often occur. Care staff with greater self-efficacy towards end-of-life communication are probably more likely to have such discussions, however, there is a lack of research on self-efficacy towards end-of-life discussions among long-term care staff in Europe and related factors. OBJECTIVES: Firstly, to describe and compare the self-efficacy level of long-term care staff regarding end-of-life communication across six countries; secondly, to analyse characteristics of staff and facilities which are associated to self-efficacy towards end-of-life communication. DESIGN: Cross-sectional survey. SETTINGS: Long-term care facilities in Belgium, England, Finland, Italy, the Netherlands and Poland (n = 290). PARTICIPANTS: Nurses and care assistants (n = 1680) completed a self-efficacy scale and were included in the analyses. METHODS: Care staff rated their self-efficacy (confidence in their own ability) on a scale of 0 (cannot do at all) to 7 -(certain can do) of the 8-item communication subscale of the Self-efficacy in End-of-Life Care survey. Staff characteristics included age, gender, professional role, education level, training in palliative care and years working in direct care. Facility characteristics included facility type and availability of palliative care guidelines, palliative care team and palliative care advice. Analyses were conducted using Generalized Estimating Equations, to account for clustering of data at facility level. RESULTS: Thde proportion of staff with a mean self-efficacy score >5 was highest in the Netherlands (76.4%), ranged between 55.9% and 60.0% in Belgium, Poland, England and Finland and was lowest in Italy (29.6%). Higher levels of self-efficacy (>5) were associated with: staff over 50 years of age (OR 1.86 95% CI[1.30-2.65]); nurses (compared to care assistants) (1.75 [1.20-2.54]); completion of higher secondary or tertiary education (respectively 2.22 [1.53-3.21] and 3.11 [2.05-4.71]; formal palliative care training (1.71 [1.32-2.21]); working in direct care for over 10 years (1.53 [1.14-2.05]); working in a facility with care provided by onsite nurses and care assistants and offsite physicians (1.86 [1.30-2.65]); and working in a facility where guidelines for palliative care were available (1.39 [1.03-1.88]). CONCLUSION: Self-efficacy towards end-of-life communication was most often low in Italy and most often high in the Netherlands. In all countries, low self-efficacy was found relatively often for discussion of prognosis. Palliative care education and guidelines for palliative care could improve the self-efficacy of care staff.

Physician Visits and Recognition of Residents' Terminal Phase in Long-Term Care Facilities: Findings From the PACE Cross-Sectional Study in 6 EU Countries.

OBJECTIVES: To describe the relation between physician visits and physicians' recognition of a resident's terminal phase in long-term care facilities (LTCFs) in Belgium, England, Finland, Italy, the Netherlands, and Poland. DESIGN: In each country, a cross-sectional study was conducted across representative samples of LTCFs. Participating LTCFs reported all deaths of residents in the previous 3 months, and structured questionnaires were sent to several proxy respondents including the treating physician. SETTING AND PARTICIPANTS: 1094 residents in 239 LTCFs, about whom 505 physicians returned the questionnaire. MEASURES: Number of physician visits, the resident's main treatment goal, whether physicians recognized the resident's terminal phase and expected the resident's death, and resident and physician characteristics. RESULTS: The number of physician visits to residents varied widely between countries, ranging from a median of 15 visits in the last 3 months of life in Poland to 5 in England, and from 4 visits in the last week of life in the Netherlands to 1 in England. Among all countries, physicians from Poland and Italy were least inclined to recognize that the resident was in the terminal phase (63.0% in Poland compared to 80.3% in the Netherlands), and residents in these countries had palliation as main treatment goal the least (31.8% in Italy compared to 92.6% in the Netherlands). Overall however, there were positive associations between the number of physician visits and the recognition of the resident's terminal phase and between the number of physician visits and the resident having palliation as main treatment goal in the last week of life. CONCLUSIONS AND IMPLICATIONS: This study suggests that LTCFs should be encouraged to work collaboratively with physicians to involve them as much as possible in caring for their residents. Joint working will facilitate the recognition of a resident's terminal phase and the timely provision of palliative care.

How to achieve the desired outcomes of advance care planning in nursing homes: a theory of change.

BACKGROUND: Advance care planning (ACP) has been identified as particularly relevant for nursing home residents, but it remains unclear how or under what circumstances ACP works and can best be implemented in such settings. We aimed to develop a theory that outlines the hypothetical causal pathway of ACP in nursing homes, i.e. what changes are expected, by means of which processes and under what circumstances. METHODS: The Theory of Change approach is a participatory method of programme design and evaluation whose underlying intention is to improve understanding of how and why a programme works. It results in a Theory of Change map that visually represents how, why and under what circumstances ACP is expected to work in nursing home settings in Belgium. Using this approach, we integrated the results of two workshops with stakeholders (n = 27) with the results of a contextual analysis and a systematic literature review. RESULTS: We identified two long-term outcomes that ACP can achieve: to improve the correspondence between residents' wishes and the care/treatment they receive and to make sure residents and their family feel involved in planning their future care and are confident their care will be according to their wishes. Besides willingness on the part of nursing home management to implement ACP and act accordingly, other necessary preconditions are identified and put in chronological order. These preconditions serve as precursors to, or requirements for, accomplishing successful ACP. Nine original key intervention components with specific rationales are identified at several levels (resident/family, staff or nursing home) to target the preconditions: selection of a trainer, ensuring engagement by management, training ACP reference persons, in-service education for healthcare staff, information for staff, general practitioners, residents and their family, ACP conversations and documentation, regular reflection sessions, multidisciplinary meetings, and formal monitoring. ONCLUSIONS: The Theory of Change map presented here illustrates a theory of how ACP is expected to work in order to achieve its desired long-term outcomes while highlighting organisational factors that potentially facilitate the implementation and sustainability of ACP. We provide the first comprehensive rationale of how ACP is expected to work in nursing homes, something that has been called for repeatedly.

Nurses' perspectives on whether medical aid in dying should be accessible to incompetent patients with dementia: findings from a survey conducted in Quebec, Canada.

We conducted a survey in a random sample of 514 Quebec nurses caring for the elderly to assess their attitudes towards extending medical aid in dying to incompetent patients and to explore associated factors. Attitudes were measured using clinical vignettes featuring a hypothetical patient with Alzheimer disease. Vignettes varied according to the stage of the disease (advanced or terminal) and the presence or absence of a written request. Of the 291 respondents, 83.5% agreed with the current legislation that allows physicians to administer aid in dying to competent patients who are at the end of life and suffer unbearably. A similar proportion (83%, p = 0.871) were in favor of extending medical aid in dying to incompetent patients who are at the terminal stage of Alzheimer disease, show signs of distress, and have made a written request before losing capacity.

Perioperative COX-2 inhibitors may increase the risk of post-operative acute kidney injury.

BACKGROUND: In enhanced recovery protocols (ERP), a restrictive fluid regimen is proposed. Patients who undergo major surgery have an increased risk of post-operative acute kidney injury (AKI). This combination may pose difficulties when ERP is used for patients undergoing major surgery. The aim of this study was to evaluate whether patients undergoing pancreatic surgery and treated with a restrictive fluid regimen are at greater risk of post-operative AKI. Furthermore, if there was an increased risk of AKI, we aimed to identify its cause. METHODS: We reviewed the medical records of patients who underwent pancreatic surgery during 2014 (preERP, n = 58) and 2015 (ERP, n = 65). Fluid balance, the administration of cyclooxygenase-2 inhibitors, creatinine levels and mean arterial pressure were recorded. The Kidney Disease: Improving Global Outcomes criteria were used to define AKI. RESULTS: The incidence of AKI was higher in the ERP group than in the PreERP group (12.5% vs. 1.8%, respectively, P = 0.035). The increased incidence of AKI could not be explained by differences in comorbidities, age, pre-operative creatinine or perioperative hypotension. Administration of coxibs was higher in the ERP group and was associated with increased incidence of post-operative AKI (P = 0.018). The combination of coxibs and restrictive fluid regimen seems particularly harmful. CONCLUSION: Pancreatic surgery with a restrictive fluid regimen carries an increased risk of post-operative AKI if patients are also treated with cyclooxygenase-2 inhibitors. It is therefore suggested that in protocols including a restrictive fluid regimen for open pancreatic surgery, the use of cyclooxygenase-2 inhibitors should be avoided.

Systematic Quality Monitoring For Specialized Palliative Care Services: Development of a Minimal Set of Quality Indicators for Palliative Care Study (QPAC).

BACKGROUND: A feasibility evaluation of a comprehensive quality indicator set for palliative care identified the need for a minimal selection of these indicators to monitor quality of palliative care services with short questionnaires for the patients, caregivers, and family carers. OBJECTIVES: To develop a minimal indicator set for efficient quality assessment in palliative care. DESIGN: A 2 round modified Research ANd Development corporation in collaboration with the University of California at Los Angeles (RAND/UCLA) expert consultation. SETTING/PATIENTS: Thirteen experts in palliative care (professionals and patient representatives). MEASUREMENTS: In a home assignment, experts were asked to score 80 developed indicators for "priority" to be included in the minimal set on a scale from 0 (lowest priority) to 9 (highest priority). The second round consisted of a plenary meeting in which the minimal set was finalized. RESULTS: Thirty-nine of the 80 indicators were discarded, while 19 were definitely selected after the home assignment, and 22 were proposed for discussion during the meeting; 12 of these survived the selection round. The final minimal indicator set for palliative care consists of 5 indicators about the physical aspects of care; 6 about the psychosocial aspects of care; 13 about information, communication, and care planning; 5 about type of care; and 2 about continuity of care. CONCLUSION: A minimal set of 31 indicators reflecting all the important issues in palliative care was created for palliative care services to assess the quality of their care in a quick and efficient manner. Additional topic-specific optional modules are available for more thorough assessment of specific aspects of care.

Palliative care needs at different phases in the illness trajectory: a survey study in patients with cancer.

Despite the growing consensus on the benefits of initiating palliative care early in the disease trajectory, it remains unclear at what point palliative care needs emerge. This study investigates quality of life and unmet palliative care needs at three phases in the cancer trajectory, curative, life-prolonging and most advanced (prognosis <6 months/no further disease-modifying treatment). We collected self-reported data from 620 patients with cancer in the University Hospital of Ghent, Belgium. They completed a questionnaire on quality of life (using the EORTC QLQ-C30) and unmet care needs within the domains of palliative care. We used European reference values of the EORTC QLQ-C30 to compare the mean scores with a norm group. The groups further on in the cancer trajectory reported statistically and clinically poorer functioning compared with earlier phases, also when controlled for the effects of sex, age or type of cancer. Higher symptom burdens for fatigue, pain, dyspnoea and appetite loss were found in groups further into the trajectory, p < .001. Patients in the curative phase experienced physical symptoms and had clinically worse functioning than a European reference group. This paper demonstrates the ongoing need for oncologists to address the broader palliative care needs of patients from diagnosis onwards.

A qualitative exploration of the collaborative working between palliative care and geriatric medicine: Barriers and facilitators from a European perspective.

BACKGROUND: With an increasing number of people dying in old age, collaboration between palliative care and geriatric medicine is increasingly being advocated in order to promote better health and health care for the increasing number of older people. The aim of this study is to identify barriers and facilitators and good practice examples of collaboration and integration between palliative care and geriatric medicine from a European perspective. METHODS: Four semi-structured group interviews were undertaken with 32 participants from 18 countries worldwide. Participants were both clinicians (geriatricians, GPs, palliative care specialists) and academic researchers. The interviews were transcribed and independent analyses performed by two researchers who then reached consensus. RESULTS: Limited knowledge and understanding of what the other discipline offers, a lack of common practice and a lack of communication between disciplines and settings were considered as barriers for collaboration between palliative care and geriatric medicine. Multidisciplinary team working, integration, strong leadership and recognition of both disciplines as specialties were considered as facilitators of collaborative working. Whilst there are instances of close clinical working between disciplines, examples of strategic collaboration in education and policy were more limited. CONCLUSIONS: Improving knowledge about its principles and acquainting basic palliative care skills appears mandatory for geriatricians and other health care professionals. In addition, establishing more academic chairs is seen as a priority in order to develop more education and development at the intersection of palliative care and geriatric medicine.

International study of the place of death of people with cancer: a population-level comparison of 14 countries across 4 continents using death certificate data.

BACKGROUND: Where people die can influence a number of indicators of the quality of dying. We aimed to describe the place of death of people with cancer and its associations with clinical, socio-demographic and healthcare supply characteristics in 14 countries. METHODS: Cross-sectional study using death certificate data for all deaths from cancer (ICD-10 codes C00-C97) in 2008 in Belgium, Canada, Czech Republic, England, France, Hungary, Italy, Mexico, the Netherlands, New Zealand, South Korea, Spain (2010), USA (2007) and Wales (N=1,355,910). Multivariable logistic regression analyses evaluated factors associated with home death within countries and differences across countries. RESULTS: Between 12% (South Korea) and 57% (Mexico) of cancer deaths occurred at home; between 26% (Netherlands, New Zealand) and 87% (South Korea) occurred in hospital. The large between-country differences in home or hospital deaths were partly explained by differences in availability of hospital- and long-term care beds and general practitioners. Haematologic rather than solid cancer (odds ratios (ORs) 1.29-3.17) and being married rather than divorced (ORs 1.17-2.54) were most consistently associated with home death across countries. CONCLUSIONS: A large country variation in the place of death can partly be explained by countries' healthcare resources. Country-specific choices regarding the organisation of end-of-life cancer care likely explain an additional part. These findings indicate the further challenge to evaluate how different specific policies can influence place of death patterns.

European palliative care guidelines: how well do they meet the needs of people with impaired cognition?

OBJECTIVE: Numbers of people dying with cognitive impairment (intellectual disability (ID), dementia or delirium) are increasing. We aimed to examine a range of European national palliative care guidelines to determine if, and how well, pain detection and management for people dying with impaired cognition are covered. METHODS: Questionnaires were sent to 14 country representatives of the European Pain and Impaired Cognition (PAIC) network who identified key national palliative care guidelines. Data was collected on guideline content: inclusion of advice on pain management, whether cognitively impaired populations were mentioned, assessment tools and management strategies recommended. Quality of guideline development was assessed with the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. RESULTS: 11 countries identified palliative care guidelines, 10 of which mentioned pain management in general. Of these, seven mentioned cognitive impairment (3 dementia, 2 ID and 4 delirium). Half of guidelines recommended the use of pain tools for people with cognitive impairment; recommended tools were not all validated for the target populations. Guidelines from the UK, the Netherlands and Finland included most information on pain management and detection in impaired cognition. Guidelines from Iceland, Norway and Spain scored most highly on AGREE rating in terms of developmental quality. CONCLUSIONS: European national palliative care guidelines may not meet the needs of the growing population of people dying with cognitive impairment. New guidelines should consider suggesting the use of observational pain tools for people with cognitive impairment. Better recognition of their needs in palliative care guidelines may drive improvements in care.

Careful monitoring of the use of sedative drugs at the end of life: the role of Epidemiology. The ITAELD study.

BACKGROUND: Sedative drugs are often used at the end of life for different clinical indications, and sometimes sedation is not interrupted until the patient dies. The aim of this study was to estimate the prevalence of patients who died while deeply sedated in Italy in 2007. METHODS: Cross-sectional survey which asked physicians about the last death that occurred among their assisted patients during the last year, and about their attitudes towards end-of-life decisions. All general practitioners (N=5,710) and a random sample of hospital physicians (N=8,950) from 14 Italian provinces were invited to participate. RESULTS: The response rate was 20%. Among 1855 reported deaths, 1466 (79.2%) were classified by physicians as expected or non-sudden; 18.2% of these expected or non-sudden deaths occurred while the patient was deeply sedated. GPs were the least likely to report deep sedation, whereas anesthetists were the most likely. In 8% of cases, sedation occurred along with an abrupt increase in the dosage of opioids during the last day of life, reaching a dosage considered higher than necessary by the doctor. No association with positive attitudes of the physician towards physician assisted death was found, whereas reporting sedation was associated with a positive attitude towards respecting the choice of relatives to forgo life-sustaining treatment in the case of an incompetent patient. CONCLUSION: Our study confirms the high prevalence of patients in Italy who die while being deeply sedated and shows that different practices may converge under the same label. Careful descriptive language is needed.

Análise e validação do procedimento de manipulação de cápsulas por encapsulamento manual por nivelamento / Analysis and validation of manual filling procedure for capsules

Entre as formas farmacêuticas sólidas de uso oral mais preparadas nas farmácias magistrais está a cápsula gelatinosa dura. O processo de manipulação de cápsulas apresenta alguns pontos críticos como a mistura e o fluxo dos pós, que podem interferir na obtenção de cápsulas na dose certa. Assim o objetivo foi analisar e validar o procedimento de manipulação de cápsulas por encapsulamento manual por nivelamento, considerando as características de fluxo e dose das formulações magistrais. A seleção dos produtos farmacêuticos (6) foi baseada na dose, fluxo e metodologia analítica validada por UV. A validação do processo consistiu na análise do peso médio, uniformidade de dose e teor de cinco lotes de cada produto preparados por dois manipuladores. Foi elaborado um procedimento escrito pelo método de nivelamento manual para os produtos metformina 500mg (MTF); paracetamol 250 mg (PCT); cetoconazol 200mg (CTZ); nimesulida 150 mg (NIM); riboflavina 20 mg(RIB) e glibenclamida 5 mg (GLB). O procedimento de manipulação foi validado para os produtos MTF, PCT,CTZ, NIM e RIB, exceto para o produto GLB, devido a reprovação de quatro lotes no teste de uniformidade de conteúdo. Os resultados nos levam a concluir que fármacos de dose acima de 20 mg (fluxo bom ou ruim) são menos susceptíveis à reprovação. O mesmo não acontece para fármacos de doses ≤ 5 mg, demonstrando que quanto menor a dose, maior a dificuldade de obter um produto na dose correta. Também foi possível verificar que o manipulador interfere na obtenção do produto de qualidade...

Among the solid dosage forms for oral use prepared regularly in compounding pharmacies is the hard gelatin capsule. The process of com pounding capsuleshas some critical features, such as the mixing and flow of powders, which can interfere with the production of capsules containing the right dose. Thus, the aim here was to analyze and validate the procedure for encapsulation of the dose by manual spreading of the formulated powder in relation to the flow characteristics and dose of the compounding formulas. The selection of the 6 pharmaceutical products was based on dose, flow and existence of a validated method of analysis by UV spectroscopy. The validation process consisted of the analysis of average weight, uniformity of dose and content of five batches of each product prepared by two handlers. A written operating procedure was prepared for the method of manual encapsulation by spreading, for capsules of 500 mg metformine (MTF), 250 mg paracetamol (PCT), 200 mg ketoconazole (CTZ), 150mg nimesulide (NIM), 20 mg riboflavin (RIB) and 5mg glibenclamide (GLB). The procedure was validated for compounding the products MTF, PCT, CTZ, NIM and RIB, but not for the product GLB, as 4 lots were rejected in the test for uniformity of content. The results lead us to conclude that, for drug doses above 20 mg (with good or bad flow), this filling procedure is less susceptible to failure. The same is not true for drugs with doses ≤ 5 mg, showing that the smaller the dose, the harder it is to produce a capsule in the correct dose. It was also observed that the handler interferes with the quality of the capsules compounded, according to official pharmaceutical criteria...

Chitin-calcium alginate composite fibers for wound care dressings spun from ionic liquid solution.

Chitin-calcium alginate composite fibers were prepared from a solution of high molecular weight chitin extracted from shrimp shells and alginic acid in the ionic liquid 1-ethyl-3-methylimidazolium acetate by dry-jet wet spinning into an aqueous bath saturated with CaCO3. The fibers exhibited a significant proportion of the individual properties of both calcium alginate and chitin. Ultimate stress values were close to values obtained for calcium alginate fibers, and the absorption capacities measured were consistent with those reported for current wound care dressings. Wound healing studies (rat model, histological evaluation) indicated that chitin-calcium alginate covered wound sites underwent normal wound healing with re-epithelialization and that coverage of the dermal fibrosis with hyperplastic epidermis was consistently complete after only 7 days of treatment. Using a single patch per wound per animal during the entire study, all rat wounds achieved 95-99% closure by day 10 with complete wound closure by day 14.

A new concept affecting restoration of inflammation-reactive astrocytes.

Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the µ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the µ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1ß, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1ß. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.

Naloxone in ultralow concentration restores endomorphin-1-evoked Ca²âº signaling in lipopolysaccharide pretreated astrocytes.

Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous µ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca²âº responses. EM-1 stimulated the µ-opioid receptor from 10⁻¹5 M up to 10⁻4 M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the µ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca²âº responses. However, a combination of ultralow concentration naloxone (10⁻¹² M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca²âº responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the µ-opioid receptor coupled G(s) protein, and that PTX should block the µ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca²âº transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca²âº transients were oscillated. To restore the EM-1-evoked Ca²âº transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca²âº transients.

Unusual microbes in asthma exacerbation: Alcaligenes xylosoxidans and Leishmania.

Asthma is a chronic inflammatory condition characterised by a variable degree of airflow limitation. Exacerbations during the course of asthma often occur due to environmental factors or infectious, mostly viral, aetiology. The present study reports the case of a 61-yr-old male with severe asthma hospitalised due to increasing respiratory distress. Since recovery was delayed despite anti-obstructive/anti-inflammatory and antibiotic therapy, further diagnostic procedures, including bronchoscopy, were performed in order to attempt to identify the cause of the worsening respiratory condition. The surprising finding consisted of a rare coincidence of concomitant infection with the bacterial pathogen Alcaligenes xylosoxidans, grown from bronchoalveolar lavage fluid, and the protozoan parasite Leishmania spp., revealed by histopathological examination of bronchial mucosal biopsy specimens. This is the first report of an isolated bronchial mucosal involvement of Leishmania in an HIV-negative asthma patient following brief exposure in Leishmania-endemic regions. Further, to the best of the present authors' knowledge, this represents the first description of A. xylosoxidans in asthma, although it is questionable whether it was an infection or colonisation. The present observation identifies previously unreported microbial pathogens associated with asthma exacerbation. Further, the report highlights the importance of obtaining a thorough travel history and applying invasive diagnostic procedures in circumstances of treatment failure, even under unfavourable conditions.