Do health expenditures affect under-five mortality and life expectancy in the ECOWAS sub-Region?

This research explored the effect of health expenditures on health outcomes in the Economic Community of West African States (ECOWAS). The study employed panel data from 2001 to 2020 of all ECOWAS member States (15 countries) and tested the datasets for the presence of a unit root after the descriptive statistics analysis had been carried out. Based on the result of the Augmented Dickey-Fuller stationarity test, the Fully Modified Ordinary Least Squares (FMOLS) method was applied. The result showed that public health expenditure was statistically significant and indirectly related to life expectancy. On the other hand, public health expenditure, private health expenditure and external health expenditure were significantly related with infant mortality. Public health expenditure was found to be directly related to infant mortality while private health and external health expenditures were negatively related. In the light of the above findings, it is recommended that policymakers in the ECOWAS region should devote a higher proportion of their annual budgets to healthcare as a strategy to improve health outcomes, reduce under-five mortality rates, and increase life expectancy in the region.

Cette recherche a exploré l'effet des dépenses de santé sur les résultats de santé dans la Communauté économique des États de l'Afrique de l'Ouest (CEDEAO). L'étude a utilisé des données de panel de 2001 à 2020 de tous les États membres de la CEDEAO (15 pays) et a testé les ensembles de données pour la présence d'une racine unitaire après la réalisation de l'analyse statistique descriptive. Sur la base du résultat du test de stationnarité augmentée de Dickey-Fuller, la méthode des moindres carrés ordinaires entièrement modifiés (FMOLS) a été appliquée. Le résultat a montré que les dépenses publiques de santé étaient statistiquement significatives et indirectement liées à l'espérance de vie. En revanche, les dépenses de santé publique, les dépenses de santé privées et les dépenses de santé externes étaient significativement liées à la mortalité infantile. Il a été constaté que les dépenses de santé publique étaient directement liées à la mortalité infantile, tandis que les dépenses de santé privées et les dépenses de santé externes étaient négativement liées. À la lumière des conclusions ci-dessus, il est recommandé que les décideurs politiques de la région de la CEDEAO consacrent une plus grande proportion de leurs budgets annuels aux soins de santé en tant que stratégie visant à améliorer les résultats sanitaires, à réduire les taux de mortalité des moins de cinq ans et à augmenter l'espérance de vie dans la région.

Audio/visual recording of doctors in hospitals: Guideline from the Association of Anaesthetists.

Guidelines are presented that summarise the legal position regarding the audio/visual recording of doctors and others in hospitals. In general, there are few, if any, legal grounds for refusing a request by patients to record procedures and/or discussions with clinicians, although some staff may feel uncomfortable being recorded. Trusts and others are advised to draw up local policies and ensure staff and patients are adequately informed.

Guidelines on suicide amongst anaesthetists 2019.

Anaesthetists are thought to be at increased risk of suicide amongst the medical profession. The aims of the following guidelines are: increase awareness of suicide and associated vulnerabilities, risk factors and precipitants; to emphasise safe ways to respond to individuals in distress, both for them and for colleagues working alongside them; and to support individuals, departments and organisations in coping with a suicide.

Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial.

Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single-centre, prospective, open-label, randomised, parallel-arm, active-control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l(-1) [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97-8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.

Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) that harbours a BRAF V600E mutation (BRAF MT) is associated with poorer outcomes. However, whether this mutation is predictive of treatment benefit from anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is uncertain. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) published up to July 2014 that evaluated the effect of BRAF MT on the treatment benefit from anti-EGFR mAbs for mCRC. RESULTS: Seven RCTs met the inclusion criteria for assessment of overall survival (OS), whereas eight RCTs met the inclusion criteria for assessment of progression-free survival (PFS). For RAS WT/BRAF MT tumours, the hazard ratio for OS benefit with anti-EGFR mAbs was 0.97 (95% CI; 0.67-1.41), whereas the hazard ratio was 0.81 (95% CI; 0.70-0.95) for RAS WT/BRAF WT tumours. However, the test of interaction (P=0.43) was not statistically significant, highlighting that the observed differences in the effect of anti-EGFR mAbs on OS according to the BRAF mutation status may be due to chance alone. Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 0.86 (95% CI; 0.61-1.21) for RAS WT/BRAF MT tumours as compared with 0.62 (95% CI; 0.50-0.77) for RAS WT/BRAF WT tumours (test of interaction, P=0.07). INTERPRETATION: This meta-analysis demonstrates that there is insufficient evidence to definitively state that RAS WT/BRAF MT individuals attain a different treatment benefit from anti-EGFR mAbs for mCRC compared with RAS WT/BRAF WT individuals. As such, there are insufficient data to justify the exclusion of anti-EGFR mAb therapy for patients with RAS WT/BRAF MT mCRC.

Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials.

BACKGROUND: Monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) prolong survival in metastatic colorectal cancer (mCRC) Kirsten rat sarcoma viral oncogene (KRAS) exon 2 wild-type tumors. Recent evidence has suggested that other RAS mutations (in exons 3 and 4 of KRAS and exons 2, 3 and 4 of a related gene, NRAS) may also be predictive of resistance. METHODS: Systematic review and meta-analysis of randomized, controlled trials (RCTs) evaluating anti-EGFR mAbs that have assessed tumors for new RAS mutations. Tumors with the new RAS mutations were compared with both tumors without any RAS mutations and tumors with KRAS exon 2 mutations with respect to anti-EGFR treatment progression-free survival (PFS) and overall survival (OS) benefit. RESULTS: Nine RCTs comprising a total of 5948 participants evaluated for both KRAS exon 2 and new RAS mutations met the inclusion criteria. Approximately 20% of KRAS exon 2 wild-type tumors harbored one of the new RAS mutations. Tumors without any RAS mutations (either KRAS exon 2 or new RAS mutations) were found to have significantly superior anti-EGFR mAb PFS (P < 0.001) and OS (P = 0.008) treatment effect compared with tumors with any of the new RAS mutations. No difference in PFS or OS benefit was evident between tumors with KRAS exon 2 mutations and tumors with the new RAS mutations. Results were consistent between different anti-EGFR agents, lines of therapy and chemotherapy partners. Anti-EGFR mAb therapy significantly improved both PFS {hazard ratio 0.62 [95% confidence interval (CI) 0.50-0.76]} and OS [hazard ratio 0.87 (95% CI 0.77-0.99)] for tumors without any RAS mutations. No PFS or OS benefit was evident with use of anti-EGFR mAbs for tumors harboring any RAS mutation (P > 0.05). CONCLUSION: Tumors harboring one of the new RAS mutations are unlikely to significantly benefit from anti-EGFR mAb therapy in mCRC.

Machete-cut injuries are occurring in the maxillofacial region in Zaria, Nigeria.

Five cases of machete cut injuries to the maxillofacial region seen over a period of 8 months (January-September, 2012), at the Maxillofacial Unit of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, are presented. The severity of the injuries is evident from the extent of tissue disruption as shown in the pictures. The immediate threats to life in the cases were hemorrhage and airway obstruction. Surgical repairs were performed under local anesthetic infiltration in three cases while the rest were performed under general anesthesia. There was no nerve repair done due to lack of facilities, although, adequate apposition of soft and hard tissues were achieved. Four patients had rapid postoperative recovery in our facility while one absconded after wound debridement and repair was achieved. Two patients who had nerve injuries were followed-up to monitor recovery of the injured nerves. There was no tetanus, gangrene, pseudoaneurysm or death recorded in our cases. There is a need for relevant authorities to check the occurrence of this kind of injury, especially as the weapon used is a house-hold tool, which is readily available and accessible to all and sundry.

A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy.

Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to metabolic changes. Here we show that, upon phosphate starvation, the metabolite sensor Pho81 interacts with the adaptor subunit Atg11 at the AKC via an Atg11/FIP200 interaction motif to modulate pexophagy by virtue of its conserved phospho-metabolite sensing SPX domain. Notably, core AKC components Atg13 and Atg17 are dispensable for phosphate starvation-induced autophagy revealing significant compositional and functional plasticity of the AKC. Our data indicate that, instead of functioning as a selective autophagy receptor, Pho81 compensates for partially inactive Atg13 by promoting Atg11 phosphorylation by Atg1 critical for pexophagy during phosphate starvation. Our work shows Atg11/FIP200 adaptor subunits bind not only selective autophagy receptors but also modulator subunits that convey metabolic information directly to the AKC for autophagy regulation.

Cytochrome P450 2S1 depletion enhances cell proliferation and migration in bronchial epithelial cells, in part, through modulation of prostaglandin E(2) synthesis.

Cytochromes P450 (P450s) contribute to the metabolic activation and inactivation of various endogenous substrates. Despite years of research, the physiological role of CYP2S1 remains unknown. CYP2S1 has demonstrated NADPH P450-reductase-independent metabolism of cyclooxygenase (COX)-derived prostaglandins [e.g., prostaglandin G(2) (PGG(2))] at nanomolar concentrations. Arachidonic acid is converted to prostaglandin precursors [PGG(2) and prostaglandin H(2) (PGH(2))] through COX. These precursors are used to synthesize numerous prostanoids, including PGE(2). Prostaglandin E(2) (PGE(2)) promotes cell proliferation and cell migration and inhibits apoptosis. CYP2S1 metabolism of PGG(2) presumably sequesters PGG(2) and PGH(2), making them unavailable for synthesis of prostanoids such as PGE(2). Whether CYP2S1 contributes to prostaglandin metabolism and influences cell physiological remains to be determined. The purpose of this study was to evaluate the physiological role of CYP2S1, if any, in human bronchial epithelial cells [SV40-derived bronchial epithelial cell line (BEAS-2B)]. To do this, we used small interfering RNA to deplete CYP2S1 mRNA and protein by approximately 75% and evaluated the impact of CYP2S1 depletion on cell proliferation and migration. CYP2S1 depletion enhanced both cell proliferation and migration in BEAS-2B cells. Consistent with the proposed role of CYP2S1 in PGE(2) synthesis, the reduction in CYP2S1 expression doubled intracellular PGE(2) levels. Pharmacological administration of PGE(2) enhanced cell proliferation in BEAS-2B cells but failed to promote migration. Our data reveal an important role for CYP2S1 in the regulation of cell proliferation and migration, occurring in part through modulation of prostaglandin synthesis.

Manganese in the upper Severn mid-Wales.

The concentrations of manganese (Mn) in the Upper River Severn (the Plynlimon catchments) are examined in relation to rainfall, cloud water, throughfall, stemflow and stream water concentrations where there is over 20 years of monitoring data available. Manganese concentrations are particularly low in rainfall and cloud water, with maximum concentrations occurring under low volumes of catch due to atmospheric "washout" of contaminants and dry deposition. There is strong Mn enrichment in throughfall and stemflow and this is probably linked to cycling through the vegetation. Manganese in the streams and groundwaters are primarily supplied from within-catchment sources. The highest concentrations occur within the tree canopy probably due to element cycling and in groundwaters due to mobilisation from the rock. Manganese concentrations in streams are at their lowest during spring and summer following long dry spells, with rapid increases following subsequent rain. There is no clear long-term trend in Mn concentration in the streams although there are increases in Mn concentrations for years when there is extensive felling of spruce plantation forest and in 1995 following a more extensive dry period. New high resolution monitoring picks up the effects of the rising limb of the hydrograph when concentrations rapidly increase, diurnal patterns during summer low-flow periods and contrasting dynamics between moorland and forested catchments.

Production of cold bromine atoms at zero mean velocity by photodissociation.

The production of a translationally cold (T < 1 K) sample of bromine atoms with estimated densities of up to 10(8) cm(-3) using photodissociation is presented. A molecular beam of Br(2) seeded in Kr is photodissociated into Br + Br* fragments, and the velocity distribution of the atomic fragments is determined using (2 + 1) REMPI and velocity map ion imaging. By recording images with varying delay times between the dissociation and probe lasers, we investigate the length of time after dissociation for which atoms remain in the laser focus, and determine the velocity spread of those atoms. By careful selection of the photolysis energy, it is found that a fraction of the atoms can be detected for delay times in excess of 100 µs. These are atoms for which the fragment recoil velocity vector is directly opposed and equal in magnitude to the parent beam velocity leading to a resultant lab frame velocity of approximately zero. The FWHM velocity spreads of detected atoms along the beam axis after 100 µs are less than 5 ms(-1), corresponding to temperatures in the milliKelvin range, opening the possibility that this technique could be utilized as a slow Br atom source.

The biogeochemistry of arsenic in a remote UK upland site: trends in rainfall and runoff, and comparisons with urban rivers.

Ten years of monitoring of rainfall and streams in the remote acidic and acid sensitive moorland and afforested moorland of upland mid-Wales reveals concentrations of arsenic (As) typically <1 µg L(-1). On average, the lowest concentrations occur within rainfall and they have declined over time probably in response to reductions in global emissions. There is a corresponding reduction within the streams except for forested systems where concentrations up to doubled following clear-fell. Within the streams there are both annual cycling and diurnal cycling of As. The annual cycling gives maxima during the summer months and this probably reflects the importance of groundwater inputs and mineralisation/desorption from the surface soil layers. Correspondingly, the diurnal cycling occurs during the summer months at low flow periods with As concentrations highest in the afternoon/evening. For the urban/industrial basins of northern England with historically a much higher As deposition, land contamination and effluent discharges, comparative data indicate As concentrations around three fold higher: strong seasonal patterns are observed for the same reasons as with the uplands. Across the sites, the As concentrations are over an order of magnitude lower than that of environmental concern. Nonetheless, the results clearly show the effects of declining emissions on rainfall deposition and some indication of areas of historic contamination. Arsenic is mainly present in the <0.45 fraction, but cross-flow filtration indicates that approx. 43% is in the colloidal phase at the clean water sites, and 16% in the colloidal phase at the contaminated sites. Part of this colloidal component may well be associated with organic carbon.

Testing the use of septum-capped vials for 13C-isotope abundance analysis of carbon dioxide.

Studying ecosystem processes in the context of carbon cycling and climate change has never been more important. Stable carbon isotope studies of gas exchange within terrestrial ecosystems are commonly undertaken to determine sources and rates of carbon cycling. To this end, septum-capped vials ('Exetainers') are often used to store samples of CO(2) prior to mass spectrometric analysis. To evaluate the performance of such vials for preserving the isotopic integrity (delta(13)C) and concentration of stored CO(2) we performed a rigorous suite of tests. Septum-capped vials were filled with standard gases of varying CO(2) concentrations (approximately 700 to 4000 ppm), delta(13)C values (approx. -26.5 to +1.8 per thousand(V-PDB)) and pressures (33 and 67% above ambient), and analysed after a storage period of between 7 and 28 days. The vials performed well, with the vast majority of both isotope and CO(2) concentration results falling within the analytical uncertainty of chamber standard gas values. Although the study supports the use of septum-capped vials for storing samples prior to mass spectrometric analysis, it does highlight the need to ensure that sampling chamber construction is robust (air-tight).

Background wet deposition of mercury in Great Britain.

Precipitation samples have been collected on a monthly basis from a network of 10 sites in Great Britain (GB) in order to estimate background mercury (Hg) deposition in the rural environment. Collection started in February 2005 and results presented here cover the period up to June 2009. The annual volume-weighted mean (AVWM) Hg concentrations range from 1.0 ng L(-1) at Cockley Beck in the Lake District in 2006 to 8.8 ng L(-1) at Heigham Holmes on the Norfolk Coast England in 2008. The largest validated solution concentrations were 33.7 ng L(-1) Hg measured at Cockley Beck in May 2008. The large difference in rainfall amount between sites means that the remote site at Cockley Beck has both the lowest long-term AVWM concentration (1.6 ng L(-1)) and the greatest annual flux is greatest at 43 mg ha(-1) yr(-1). Predicted deposition tends to be much greater in western Britain where the greater rainfall occurs. Because some observations are very close to the analytical detection limit (1.0 ng L(-1)), rigorous cleaning procedures, the use of replicate samplers to monitor contamination, and the inclusion of 'bottle blanks' are required to obtain valid measurements of Hg in the bulk deposition. Deposition in rural sites is equivalent to about 10% of the estimated magnitude of known emissions in GB.

Mercury in rivers in NW England: from rural headwaters to the heartlands of the historic industrial base.

Total mercury (T-Hg) concentrations in rivers are described across a rural to urban/industrial and agricultural landscape gradient in NW England. T-Hg ranges between 0.2 and 230 ng L(-1). The regional median was 3.6 ng L(-1) with individual river medians ranging between 1.9 and 8.3 ng L(-1). Median T-Hg concentrations were sometimes moderately higher for the lowland areas and at higher flows. Our estimates suggest that the Ribble estuary receives 9.2 kg y(-1) and the Wyre estuary 0.7 kg y(-1). In order to examine regional inputs from urban/industrial components, regression analysis was undertaken by comparing three types of hydrochemical signature: suspended sediments (SS), which provide a measure of the particulate component, dissolved organic carbon (DOC) that provides an indication of humic/fulvic acids that are part of the organic colloids and strong chelating agents, and boron a marker of sewage effluents and population density. The results show high positive relationships of T-Hg with both SS and DOC, but no relationship with the urban/industrial signal. The regression analysis with T-Hg indicated on average a gradient of 0.33 ng mg(-1) for DOC and 0.2 ng mg(-1) for SS. They indicate the primary importance of a diffuse source of T-Hg. For the upland areas and cleaner river systems, the linkages between T-Hg and DOC were particularly strong, while for the lowland areas, the linkage with SS proved stronger. Analysis of a latter subset of data that partition the SS into organic and inorganic fractions indicated that the T-Hg was primarily linked with the organic fraction. Indeed, multiple regression of T-Hg with DOC and POM reveals gradients similar to other parts of the World.

Clinical outcomes of combined surgical treatment of medial epicondylitis and cubital tunnel syndrome.

Surgical results for treatment of medial epicondylitis and cubital tunnel syndrome are generally satisfactory when performed alone. However, our experience suggests a combined procedure is associated with inferior outcomes. A retrospective review was conducted of consecutive surgical cases of medial epicondylectomy/debridement and ulnar nerve decompression during a single operation at our institution from March 2008 to February 2017 using CPT codes. Thirty combined procedures were identified in 29 patients. Fourteen patients and 15 elbows returned to clinic for evaluation at average 4.3 years after surgery (8 men, 6 women, mean age 45.1 years). A Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analogue pain scale (VAS), and physical examination were performed. The data was stratified by type of ulnar nerve procedure and analyzed. Three of fifteen elbows underwent in situ ulnar nerve decompression, and twelve of 15 had transposition, five subcutaneous and seven submuscular. The mean DASH score for in situ decompression was significantly higher than that of transposition (68.2 vs. 13.1). The average visual pain score for patients whom underwent in situ decompression was significantly higher than that of those with ulnar nerve transposition (8.0 vs. 1.2). All other physical exam measures demonstrated no significant difference between the two groups. In situ ulnar nerve decompression in the setting of medial epicondylectomy/debridement may be associated with inferior clinical outcomes in comparison to ulnar nerve transposition. Further studies are needed to validate the results of our study and inform management.

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.

Monodentate phosphine substitution in [Pd(κ3-dppf)(PR3)][BF4]2 (dppf = 1,1'-bis(diphenylphosphino)ferrocene) compounds.

The ligand 1,1'-bis(diphenylphosphino)ferrocene (dppf) is commonly employed in a variety of catalytic systems. There are a variety of coordination modes known for dppf, the least studied being the κ3 coordination mode, in which both phosphorus atoms and the iron atom of dppf interact with another metal center. One such compound is the previously reported [Pd(κ3-dppf)(PPh3)]2+. A series of related compounds, [Pd(κ3-dppf)(P(p-C6H4R)3)]2+ (R = OCH3, CH3, F and CF3), has been synthesized and characterized. The X-ray crystal structure of [Pd(dppf)(P(p-C6H4F)3)][BF4]2 was determined. Electrochemical and computational studies indicate that the electron donor ability of the P(p-C6H4R)3 ligands influences the properties of these compounds. Substitution reactions of the P(p-C6H4R)3 ligands have been examined, and, in general, the more electron donating P(p-C6H4R)3 ligands completely replace the less electron donating ones. The kinetics of the reaction of [Pd(κ3-dppf)(P(p-C6H4F)3)]2+ with P(p-C6H4OCH3)3 indicate that the reaction proceeds through a dissociative mechanism, contrary to the associative substitutions prevalent in square planar palladium(ii) chemistry.

The use of vitamin A-deficient diets and jugular vein ligation to increase intracranial pressure in chickens (Gallus gallus).

A technique was developed to record intracranial cerebrospinal fluid pressure (iCSFp) in chicks and mature chickens. Using that procedure, 2 methods were found to effect a significant elevation in intracranial pressure: 1) feeding a purified diet to roosters for 40 d containing 25% of the bird's requirement for vitamin A, and 2) ligating both jugular veins in birds. The purified diet significantly reduced plasma retinol levels from 1.080 to 0.046 microg/mL, and iCSFp was significantly elevated from 63.0 to 106.0 mmH2O (P < or = 0.05). Two limitations for using hypovitaminosis A diets were capillary fragility and a cisterna magna that did not develop to the size of that structure in birds of the same age fed control diets with adequate vitamin A content. The second procedure, a reversible surgical technique, showed that within 2.5 h from jugular vein ligation, intracranial pressure rose to 109.7 mmH2O, comparable with levels attained following feeding a vitamin A deficient diet to roosters. Bilateral clamping of the jugular veins overnight resulted in an elevation of iCSFp to 127 +/- 8.86 mmH2O. Results suggest that the chicken may be a useful animal model to investigate intracranial hypertension and its accompanying headaches known to occur in humans.

Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years' continuous treatment.

OBJECTIVE: This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years. METHODS: Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification. RESULTS: Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus. CONCLUSION: Long-term treatment with pantoprazole is effective and safe.