Determinants of Adherence among Patients on Highly Active Anti-Retroviral Therapy in Lagos State, Nigeria.

BACKGROUND: Poor medication adherence in HIV treatment is a public health problem as it leads to increased morbidity and mortality, as well as the development of drug resistance. There is limited information on the determinants of adherence among people living with HIV/AIDS especially in sub-Saharan Africa. This study aimed at assessing the determinants of adherence to HAART among people living with HIV/AIDS in Lagos State, Nigeria. METHODS: A descriptive cross-sectional survey was conducted among 302 respondents selected from three public health facilities across the state. The study instrument was an interviewer-administered questionnaire adapted from the Medication Adherence Report Scale (MARS). Data analysis was performed using Epi Info software. Logistic regression analysis was used to identify the determinants of adherence. Level of significance for all the tests was set at p-value <0.05. RESULTS: Seventy percent of respondents reported being adherent to medication. There were statistically significant associations between respondents' age, having children, good knowledge of HIV and medication adherence. In addition, it was observed that the type of anti-retroviral (ARV) drug schedule, never missing an appointment, belonging to a support group and disclosure of status were associated with HAART adherence. Controlling for other variables, those that had disclosed their status were twice as likely to adhere to HIV medication (aOR: 2.3; 95% CI: 1.1-4.8). Also, those who had never missed a clinic appointment were three times more likely to adhere to prescribed medication (aOR: 3.4; 95% CI: 1.7-6.5). CONCLUSION: Disclosure of HIV status and clinic attendance were key determinants of adherence among patients on HAART in Lagos, Nigeria.

RÉSUMÉ: La mauvaise adhésion aux médicaments dans le traitement du VIH est un problème de santé publique car elle entraîne une augmentation de la morbidité et de la mortalité, ainsi que le développement d'une résistance aux médicaments. Il existe peu d'informations sur les déterminants de l'adhésion chez les personnes vivant avec le VIH/SIDA, en particulier en Afrique subsaharienne. Cette étude visait à évaluer les déterminants de l'adhésion au HAART chez les personnes vivant avec le VIH/SIDA dans l'État de Lagos, au Nigéria. MÉTHODES: Une enquête transversale descriptive a été menée auprès de 302 répondants sélectionnés dans trois établissements de santé publics à travers l'État. L'instrument de l'étude était un questionnaire administré par l'intervieweur, adapté de la Medication Adherence Report Scale (MARS). L'analyse des données a été réalisée à l'aide du logiciel Epi Info. Une analyse de régression logistique a été utilisée pour identifier les déterminants de l'adhésion. Le niveau de signification pour tous les tests a été fixé à une valeur p < 0,05. RÉSULTATS: Soixante-dix pour cent des répondants ont déclaré être adhérents aux médicaments. Il y avait des associations statistiquement significatives entre l'âge des répondants, le fait d'avoir des enfants, une bonne connaissance du VIH et l'observance du traitement. De plus, il a été observé que le type d'horaire des médicaments antirétroviraux (ARV), ne jamais manquer un rendez-vous, appartenir à un groupe de soutien et la divulgation du statut étaient associés à l'adhésion au HAART. En contrôlant les autres variables, ceux qui avaient divulgué leur statut étaient deux fois plus susceptibles d'adhérer aux médicaments anti-VIH (aOR : 2,3 ; IC à 95 % : 1,1­4,8). De plus, ceux qui n'avaient jamais manqué un rendez-vous à la clinique étaient trois fois plus susceptibles de respecter les médicaments prescrits (aOR : 3,4 ; IC à 95 % : 1,7-6,5). CONCLUSION: La divulgation du statut VIH et la fréquentation de la clinique étaient des déterminants clés de l'adhésion chez les patients sous HAART à Lagos, au Nigeria. MOTS CLÉS: Déterminants, compliance médicamenteuse, Thérapie antirétrovirale, PVVIH.

MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC. METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC. RESULTS: Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml(-1)) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047). CONCLUSIONS: Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.

Pseudotannins self-assembled into antioxidant complexes.

Natural tannins are attractive as building blocks for biomaterials due to their antioxidant properties and ability to form interpolymer complexes (IPCs) with other macromolecules. One of the major challenges to tannin usage in biomedical applications is their instability at physiological conditions and a lack of control over the purity and reactivity. Herein, we report the synthesis and characterization of tannin-like polymers with controlled architecture, reactivity, and size. These pseudotannins were synthesized by substituting linear dextran chains with gallic, resorcylic, and protocatechuic pendant groups to mimic the structure of natural hydrolysable tannins. We demonstrate that these novel materials can self-assemble to form reductive and colloidally stable nanoscale and microscale particles. Specifically, the synthesis, turbidity, particle size, antioxidant power, and cell uptake of IPCs derived from pseudotannins and poly(ethylene glycol) was evaluated.

An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae.

AIM: The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula. METHOD: Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost. RESULTS: Seventy-one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was €5439 ± €2629 and €7957 ± €5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023). CONCLUSION: Anal fistula plug and ERAF were equally effective in treating fistula-in-ano, but AFP has a mean cost saving of €2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.

Barriers and enablers to implementing police mental health co-responder programs: A qualitative study using the consolidated framework for implementation research.

Background: Police and mental health co-responder programs operate internationally and can be effective in providing timely and appropriate assessment, brief intervention, and referral services for people experiencing mental health crises. However, these models vary greatly, and little is known about how the design and implementation of these programs impacts their effectiveness. Method: This study was a qualitative, post hoc implementation determinant evaluation of mental health co-responder units in Brisbane, Australia, comprising of verbal or written interviews with police and mental health staff with an on-road role in the co-responder units, and their managers. The Consolidated Framework for Implementation Research was used to identify barriers and enablers to the program's implementation and effectiveness. Results: Participants (n = 30) from all groups felt strongly that the co-responder units are a substantial improvement over the usual police management of mental health crisis cases, and lead to better outcomes for consumers and the service. Enablers included an information-sharing agreement; the Mental Health Co-Responder (MHCORE) program's compatibility with existing police and mental health services; and the learning opportunity for both organizations. Barriers included cultural differences between the organizations, particularly risk-aversion to suicidality for police and a focus on least-restrictive practices for health; extensive documentation requirements for health; and a lack of specific mental health training for police. Conclusions: Using an evidence-based implementation science framework enabled identification of a broad range of contextual barriers and enablers to implementation of police mental health co-responder programs. Adapting the program to address these barriers and enablers during the planning, implementation, monitoring, and evaluation phases increases the likelihood of the service's effectiveness. These findings will inform the spread and scale of the co-responder program across Queensland, and will be relevant to police districts internationally considering implementing a co-responder program.

A large and rising proportion of calls to police relate to mental health crises, however police lack the resources, knowledge, training and supports to effectively address these crises. In Brisbane, Australia people in mental health crisis who are attended by police are routinely transported under an Emergency Examination Authority to a hospital emergency department. This is time-consuming for both the consumer and police, may be stressful or distressing for the consumer, and can put pressure on emergency departments. Co-responder programs team a senior mental health clinician with a senior police officer. There is evidence that a qualified and experienced mental health clinician providing people in mental health crisis with a timely assessment and brief intervention in the field, and where appropriate, referral to support services, leads to better outcomes for the consumer, reduced hospital transport, reduced time per case, and reduced overall service costs. Although many papers have been written evaluating the outcomes of these programs, few have considered factors that impact the implementation, effectiveness, and sustainment of co-responder teams. We used an implementation science approach based on the Consolidated Framework for Implementation Research to identify barriers to and enablers of mental health co-responder program implementation within an Australian metropolitan setting. Understanding these barriers and enablers allows a more streamlined, better-informed roll-out of future programs, and adaptation of existing models to improve effectiveness. The results will be relevant for any police district considering implementing a mental health co-responder program. They will also be used to inform the ongoing program.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema: protocol for a pilot study.

BACKGROUND: Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. METHODS/DESIGN: D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. DISCUSSION: MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03341676 . Registered on 14 November 2017.

Percutaneous lung ablation of pulmonary recurrence may improve survival in selected patients undergoing cytoreductive surgery for colorectal cancer with peritoneal carcinomatosis.

PURPOSE: To analyze the outcomes of patients developing pulmonary metastases (PM) following cytoreductive surgery (CRS) and perioperative intra-peritoneal chemotherapy (IPC) for colorectal cancer (CRC) with peritoneal carcinomatosis. PATIENTS AND METHODS: A retrospective analysis of patients undergoing CRS/IPC for CRC from 1996 to 2016 was performed. Lung-specific disease-free and patient overall survival was analyzed. Patients undergoing percutaneous lung ablative therapy (PLAT) for PM were compared to patients receiving systemic chemotherapy alone. RESULTS: 273 patients underwent CRS/IPC for CRC. Of these, 61 (22%) developed PM. Median time to development of PM was 8 months (range 0-52 months) and 41 patients (67%) had metachronous lesions. Twenty-one PM patients underwent PLAT, either by radio-frequency or micro-wave ablation, for an average of 3 lesions (range 1-12) and 13 (62%) had bilobar disease. The most common post-interventional complication was the development of pneumothorax (71%). Overall survival following development of PM was 18 months and higher in patients undergoing PLAT compared to those treated with systemic chemotherapy (26 vs. 14 months, p = 0.03). In eight cases (38%) local tumor recurrence developed post-PLAT. A peritoneal carcinomatosis index >10 (HR 3.48, 95% CI 1.69-7.19), presence of liver metastases (HR 2.49, 95% CI 1.24-5.03) and PLAT (HR 0.43, 95% CI 0.20-0.93) were identified as significant predictors of overall survival following diagnosis of PM. CONCLUSION: PM develop in approximately a fourth of patients undergoing CRS/IPC for CRC. Of these, about 1/3 may be eligible for PLAT. PLAT is a valuable treatment option providing good local control and potentially prolongation of overall survival.

Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization.

AIM: Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction. METHODS: In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay. RESULTS: Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014). CONCLUSIONS: A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

[Occupational scleroderma due to organic solvent exposure].

Progressive systemic sclerosis (PSS; scleroderma) is a multisystem disease characterized by inflammation, fibrosis and degeneration of the integument, with similar changes and vascular lesions in the heart, lungs, kidneys, gastrointestinal tract and synovia. Its etiology is not clear. Several occupational exposures have been implicated as potential causes of PSS and scleroderma-like diseases. Among them are vinyl chloride monomer, silica dust, epoxy resin, and benzene and other solvents, aromatic and aliphatic, specifically chlorinated (trichloroethylene, perchloroethylene and trichloromethane). We present a patient whose illness was diagnosed as occupationally induced PSS. During 13 years of work renovating carburetors he was heavily exposed to trichloromethane. To the best of our knowledge this is the first reported case of PSS due to exposure to organic solvents in Israel; very few cases have been reported from abroad.

[Energy metabolism disorders in experimental atherosclerotic chorioretinopathy]. / Narushenie énergeticheskogo obmena pri éksperimental'noi ateroskleroticheskoi khorioretinopatii.

Electron-microscopic, electron-histochemical, and biochemical studies in 12 rabbits with hypercholesterolemia revealed disorders in energy metabolism and redox processes in endotheliocytes of choroidal microvessels. These disorders resulted in functional defects of endotheliocytes, with changes in their membrane structure and disorders in ocular membrane microcirculation.

[Effect of local revascularization of choroid on ocular tissues and lipid peroxidation in experimental atherosclerotic chorioretinopathy]. / Vliianie operatsii lokal'noi revaskuliarizatsii khorioidei na tkani glaza i perekisnoe okislenie lipidov pri éksperimental'noi ateroskleroticheskoi khorioretinopatii.

Lipid composition and lipid peroxidation in ocular tissues were assessed in 42 rabbits with hypercholesterolemia. The levels of nonesterified cholesterol, diacylglycerides, nonesterified fatty acids, and of malonic dialdehyde were increased and the content of endogenous antioxidants decreased in animals with experimental atherosclerotic chorioretinopathy. Surgery (local revascularization of the vascular coating with two flaps) resulted in improvement of ocular biochemistry and microcirculation in the posterior segments of the eye and in recovery of the functional intactness of the retina and choroid.

[A morphological study of tissues in the posterior segment of the eye after modified experimental revascularization of the choroid]. / Morfologicheskoe issledovanie tkanei zadnego poliusa glaza posle modifitsirovannoi operatsii revaskuliarizatsii khorioidei, vypolnennoi v éksperimente.

Morphologic examination of ocular tissues at the site of revascularization with two flaps was carried out to detect the changes in the architectonics of these flaps' vessels, vascular coating at the site of intervention, and assess the formation of relation with the vascular system of the external tissues of the eye. Experiments were carried out on the eyes of 8 cats. All the animals were subjected to local revascularization of the vascular coating with two flaps. Enucleation was carried out 1 to 6 months after the operation. The eyes were fixed in 10% neutral formalin solution, paraffin slices and blocks were prepared, stained with hematoxylin and eosin, with pyrofucin after Van Gieson, and with toluidine blue after Lison. Histologic study of ocular tissue slices 2-3 weeks after surgery showed that the flaps introduced into the supra-arachnoidal space tightly fitted each other forming a subconjunctival-episcleral transplant in which a moderate number of newly formed vessels was detected. Three to six months after surgery vascularization of the transplant proper and around it grew more and more intensive, the number of new vessels increased with their walls looking more compact; basal membrane appeared well shaped. The walls of new vessels did not differ by structure from normal vascular walls in the vascular coating.

Mode of delivery following external cephalic version and induction of labor at term.

External cephalic version should be followed by fetal and maternal surveillance until delivery. To shorten this period of surveillance, a protocol of version at term, followed by immediate induction of labor, was adopted. The aim of the present study was to evaluate the effect of this protocol on the subsequent mode of delivery. Two hundred and ninety-one singleton breech pregnancies were included in this study. Of these, 74 cases underwent version, 75% of which were successful. Success of version compared to failed version was associated with statistically significant (p < 0.001) lower rate of cesarean sections (9% and 67%, respectively). The overall rate of abdominal deliveries in the version group (74 cases) was statistically significantly lower compared with two other groups: one composed of breech pregnancies that did not undergo versions, but would have been qualified for it, had they been referred on time (121 cases), and the other (96 cases) that did not have versions done because of contraindications to its performance (cesarean rates, 23%, 54%, and 79%, respectively; p < 0.001). It may be concluded that a policy of external cephalic version at term is effective in lowering the incidence of cesarean deliveries, and the added intervention of induction of labor does not negate this effect.

Bone alkaline phosphatase kinetics studied by a new method.

Studies of enzyme kinetics by histochemical methods has been seriously impaired by available methods. This study combines two newer methods, i.e., sectioning undecalcified bone from glycol methacrylate and the use of atomic absorpton spectrophotometry for photographic densitometry. The results indicate that the substrate concentration for zero order kinetics of the alkaline phosphatase reaction in bone is 0.5 mg/ml of substrate; and the Km of the same reaction is estimated to be 0.25 mg/ml or 0.56 mM of substrate.