Oxygen for children and newborns in non-tertiary hospitals in South-west Nigeria: A needs assessment.

BACKGROUND: Oxygen is important for the treatment of hypoxaemia associated with pneumonia, malaria, and other medical, obstetric, and surgical conditions. Access to oxygen therapy is limited in many of the high mortality settings where it would be of most benefit. METHODS: A needs assessment of 12 non-tertiary hospitals in south-west Nigeria, assessing structural, technical and clinical barriers to the provision of safe and effective oxygen therapy. RESULTS: Oxygen supply was reported to be a major challenge by hospital directors. All hospitals had some access to oxygen cylinders, which were expensive and frequently ran out. Nine (75%) hospitals used oxygen concentrators, which were limited by inadequate power supply and lack of maintenance capacity. Appropriate oxygen delivery and monitoring devices (nasal prongs, catheters, pulse oximeters) were poorly available, and no hospitals had clinical guidelines pertaining to the use of -oxygen for children. Oxygen was expensive to patients (median US$20/day) and to hospitals. Estimated oxygen demand is reported using both a constant mean-based estimate and adjustment for seasonal and other variability. CONCLUSIONS: Making oxygen available to sick children and neonates in Nigerian hospitals will require: improving detection of hypoxaemia through routine use of pulse oximetry; improving access to oxygen through equipment, training, and maintenance structures; and commitment to building hospital and state structures that can sustain and expand oxygen initiatives.

Oral Cavity Cancers: Ethnic Differences in Radiotherapy Outcomes in a Majority South Asian Leicester Community.

AIMS: Squamous cell carcinoma oral cavity cancers (SCCOCCs) have a higher reported incidence in South Asian countries. We sought to compare presenting stage and outcome by ethnicity in patients with SCCOCC treated with radical radiotherapy in a single centre in the UK. MATERIALS AND METHODS: All patients with SCCOCC treated with radical radiotherapy at an oncology department in Leicester (UK) between 2011 and 2017 were identified. Baseline demographic, clinical data and 2-year treatment outcomes were reported. RESULTS: Of the 109 patients included, 40 were South Asian and 59 were non-South Asian. South Asians had significantly poorer 2-year disease-free survival compared with non-South Asians (54.6% versus 73%, P = 0.01). CONCLUSION: Our analysis suggests that South Asians with SCCOCC have poorer outcomes despite a younger age and similar disease characteristics. Environmental, social factors and differing biology of disease may be responsible and further research is required to inform targeted interventions.

Evaluation of oxygen concentrators for use in countries with limited resources.

Seven different models of oxygen concentrators were purchased. The manufacturer's data were evaluated by a ranking method for operation at high temperature and high relative humidity, power consumption, warranty and cost. Measurements were then made of the oxygen concentration produced at maximum operating temperature. All the concentrators were CE marked and claimed compliance with the relevant Standard ISO 8359:1996. Only two models complied with their specification. On examination of the concentrators and the accompanying documents we found that compliance with 61 points listed in ISO 8359 ranged from 85% to 98%. Oxygen concentration was measured with the machines running simultaneously under both high temperature and high humidity. All models delivered low oxygen concentrations at 40 °C and 95% relative humidity. Only two models delivered >82% at 35 °C and 50% relative humidity. Concentrators intended for use in countries with limited resources should be evaluated before they are purchased, by independent experts, using the methods described herein.

Oxygen concentrators: a practical guide for clinicians and technicians in developing countries.

Hypoxaemia is a common problem causing child deaths in developing countries, but the cost-effective ways to address hypoxaemia are ignored by current global strategies. Improving oxygen supplies and the detection of hypoxaemia has been shown to reduce death rates from childhood pneumonia by up to 35%, and to be cheaper per life saved than other effective initiatives such as conjugate pneumococcal vaccines. Oxygen concentrators provide the cheapest and most consistent source of oxygen in health facilities where power supplies are reliable. To implement and sustain oxygen concentrators requires strengthening of health systems, with clinicians, teachers, administrators and technicians working together. Programmes built around the use of pulse oximetry and oxygen concentrators are an entry point for improving quality of care, and are a unique example of successful integration of appropriate technology into clinical care. This paper is a practical and up-to-date guide for all involved in purchasing, using and maintaining oxygen concentrators in developing countries.

Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia.

The Discs large (Dlg) protein of Drosophila is the prototypic member of a growing family of proteins termed membrane-associated guanylate kinase homologs (MAGUKs). The MAGUKs are composed of a series of peptide domains that include one or three DHR/PDZs, an SH3, and a region homologous to guanylate kinase (GUK). We have previously shown that the product of this gene, the Dlg protein, is localized at the septate junctions between epithelial cells, and that mutations in the gene cause neoplastic overgrowth of the imaginal discs. The dlg locus is therefore defined as a tumor suppressor gene. In this paper, we show that the Dlg protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure. It is also required for proper organization of the cytoskeleton, for the differential localization of membrane proteins, and for apicobasal polarity of epithelial cells. However, these other functions can be uncoupled from Dlg's role as a tumor suppressor since mutations in two domains of the protein, the SH3 and GUK, cause loss of normal cell proliferation control without affecting the other functions of the protein. These results suggest that, besides regulating cellular proliferation, the Dlg protein is a critical component of the septate junctions and is required for maintaining apicobasal polarity in Drosophila epithelium.

Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a situational analysis.

SETTING: Health facilities in The Gambia, West Africa. OBJECTIVES: Oxygen treatment is vital in pneumonia, the leading cause of death in children globally. There are shortages of oxygen in developing countries, but little information is available on the extent of the problem. We assessed national oxygen availability and use in The Gambia, a sub-Saharan African country. METHODS: A government-led team visited 12 health facilities in The Gambia. A modified World Health Organization assessment tool was used to determine oxygen requirements, current provision and capacity to support effective oxygen use. RESULTS: Eleven of the 12 facilities managed severe pneumonia. Oxygen was reliable in three facilities. Requirement and supply were often mismatched. Both oxygen concentrators and oxygen cylinders were used. Suboptimal electricity and maintenance made using concentrators difficult, while logistical problems and cost hampered cylinder use. Children were usually triaged by trained nurses who reported lack of training in oxygen use. Oxygen was given typically by nasal prongs; pulse oximetry was available in two facilities. CONCLUSIONS: National data showed that oxygen availability did not meet needs in most Gambian health facilities. Remedial options must be carefully assessed for real costs, reliability and site-by-site usability. Training is needed to support oxygen use and equipment maintenance.

Pulse oximetry: technology to reduce child mortality in developing countries.

The causes of hypoxaemia in children include the commonest causes of childhood illness: pneumonia and other acute respiratory infections, and neonatal illness, particularly sepsis, low birthweight, birth asphyxia and aspiration syndromes. The systematic use of pulse oximetry to monitor and treat children in resource-poor developing countries, when coupled with a reliable oxygen supply, improves quality of care and reduces mortality. Oximetry also has a well established role in surgery and anaesthesia, but in many countries children undergo surgery without the safety of oximetry monitoring. This article reviews pulse oximetry, its technical basis and its application to the medical management of childhood illness to reduce mortality in developing countries. We propose that, as a part of the work towards achieving the Millennium Development Goal 4, there should be a concerted global effort to make pulse oximetry and a reliable oxygen source available in all health facilities where seriously ill children are managed.

Hypertension, diuretics and breast cancer risk.

It is unclear whether hypertension and antihypertensive medication use are associated with breast cancer. In order to examine these associations, we conducted a case-control study among women aged 50-75 years. Breast cancer cases were ascertained via a population-based cancer registry (n=523) and controls were ascertained via random-digit-dialing (n=131). Participants completed a self-administered questionnaire which queried history of hypertension, antihypertensive medication use and risk factors. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), diabetes, smoking, alcohol use, menopausal status, family history of breast or ovarian cancer, age at first full-term pregnancy and education. History of treated hypertension was associated with significant increased risk of breast cancer (OR, 1.77; 95% CI, 1.04-3.03) and this association appeared only in women with BMI > or =25 kg/m(2) (OR, 2.30; 95% CI, 1.12-4.71). Diuretic use was also associated with elevated breast cancer risk (OR, 1.79; 95% CI, 1.07-3.01). The risk associated with diuretic use increased with duration of use (P for trend, <0.01). Use of other blood pressure medications was not found to be associated with breast cancer risk. These results support a positive association between treated hypertension, diuretic use and breast cancer risk among women aged 50-75 years.

Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases.

BACKGROUND: The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors. METHODS: Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided. RESULTS: Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0. 3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC. Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases. CONCLUSIONS: On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample.

Germ-line msh6 mutations in colorectal cancer families.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ-line mutations in other mismatch repair genes are rare. We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases, germ-line msh6 mutations were found in 6 patients (7.1% of probands analyzed; median age at diagnosis, 61 years). These mutations included a splice site mutation, a frameshift mutation, two missense mutations that were demonstrated to be loss of function mutations, and two missense mutations for which functional studies were not possible. In contrast, germ-line msh6 mutations were not found in any of the 45 sporadic cases and the 4 HNPCC cases in the population-based series or in the second series of 58 clinic-based, primarily HNPCC families. Our data suggest that germ-line msh6 mutations predispose individuals to primarily late-onset, familial colorectal carcinomas that do not fulfill classic criteria for HNPCC.

Implementation and 8-year follow-up of an uninterrupted oxygen supply system in a hospital in The Gambia.

SETTING: A 42-bed hospital operated by the Medical Research Council (MRC) Unit in The Gambia. OBJECTIVE: To devise, test and evaluate a cost-efficient uninterrupted oxygen system in the MRC Hospital. DESIGN: Oxygen cylinders were replaced with oxygen concentrators as the primary source of oxygen. An uninterruptable power supply (UPS) ensured continuity of power. Hospital staff were trained on the use of the new system. Eight years post-installation, an analysis of concentrator maintenance needs and costs was conducted and user feedback obtained to assess the success of the system. RESULTS: The new system saved at least 51% of oxygen supply costs compared to cylinders, with savings likely to have been far greater due to cylinder leakages. Users indicated that the system is easier to use and more reliable, although technical support and staff training are still needed. CONCLUSION: Oxygen concentrators offer long-term cost savings and an improved user experience compared to cylinders; however, some technical support and maintenance are needed to upkeep the system. A UPS dedicated to oxygen concentrators is an appropriate solution for settings where power interruptions are frequent but short in duration. This approach can be a model for health systems in settings with similar infrastructure.

Repopulation in irradiated pig skin: late versus early effects.

In the first 16 weeks after irradiation, two distinct waves of reaction can be observed in pig skin, the first wave (3-9 weeks) represents the expression of damage to the epithelium while the second is indicative of primary damage to the dermis, mediated through vascular injury. Following beta-irradiation with a strontium-90 applicator, a severe epithelial reaction was seen with little subsequent dermal effects. X-rays (250 kV), on the other hand, produced a minimal epithelial response at doses which led to the development of dermal necrosis after 10-16 weeks. Comparison of single doses with two equal doses separated by 28 days produced a D2-D1 value of 14.0 Gy at the doses which produced moist desquamation in 50% of fields (ED50) after strontium-90 irradiation. After X-irradiation, comparison of ED50 doses for the later dermal reaction suggested a D2-D1 value of 4.2 Gy. These values of D2-D1 for epithelial and dermal reactions in pig skin were compared with earlier data from this laboratory for similar split-dose experiments with a one-day interval. Such a comparison allowed for the estimation of the component of recovery in the present 28-day interval experiments due to repopulation. This component was found to be 6.5 Gy for the early epithelial damage, but was zero for the later dermal damage.

Split-dose recovery in epithelial and vascular-connective tissue of pig skin.

In the first 16 weeks after irradiation, two distinct waves of reaction can be observed in pig skin; the first wave (3-9 weeks) represents the expression of damage to the epithelium while the second is indicative of primary damage to the dermis, mediated through vascular injury. Following beta-irradiation with a strontium-90 applicator, a severe epithelial reaction was seen with little subsequent dermal effects. X-rays (250 kV) on the other hand, produced a minimal epithelial response at doses which led to the development of dermal necrosis after 10-16 weeks. Comparison of single doses with two equal doses separated by 24 h produced a D2-D1 value of 7.0 Gy at the doses which produced moist desquamation in 50% of fields (ED50) after strontium-90 irradiation. After X-irradiation comparison of ED50 doses for the later dermal reaction suggested a D2-D1 value of 4.5 Gy. Over this same dose range of X-rays the D2-D1 value for the first wave epithelial reaction was 3.5 Gy. These values of D2-D1 for epithelial and dermal reactions in pig skin were compared with published data and were examined in relation to the theoretical predictions of a linear quadratic model for tissue target cell survival. The results were broadly in keeping with the predictions of such a model.

Late nonstochastic changes in pig skin after beta irradiation.

Late radiation-induced changes in pig skin have been assessed following irradiation with beta-rays from a 22.5- or 15-mm-diameter 90Sr/90Y source and a 19- or 9-mm-diameter 170Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness in irradiated and normal skin. After 90Sr irradiation maximum atrophy, a dermal thickness of 40-50% of the control value, occurred at a dose of approximately 40 Gy from the 22.5-mm source and approximately 75 Gy from the 15-mm source. In the case of 170Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approximately 70 Gy, when the dermis was approximately 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin.

Nonstochastic effects of different energy beta emitters on pig skin.

Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.