Prevalence and Factors Associated with Acute Kidney Injury among Malaria Patients in Dar es Salaam: A Cross-Sectional Study.

INTRODUCTION: Falciparum malaria still remains as a major cause of morbidity and mortality worldwide. Acute kidney injury is a known complication of malaria, and it is reported to occur in up to 40% of adult patients with severe falciparum malaria in endemic regions like sub-Saharan Africa. OBJECTIVES: To determine the prevalence and factors associated with acute kidney injury among falciparum malaria patients in a tertiary level private hospital in Dar es Salaam. METHODOLOGY: In a cross-sectional study design, 104 adults with falciparum malaria were enrolled consecutively over 6 months from April to September 2015. The diagnosis of acute kidney injury (AKI) in these patients was established using the KDIGO classification criteria. The prevalence of AKI was obtained at 48 hours from admission and at day 7. Different sociodemographic and clinical parameters which were associated with acute kidney injury at 48 hours and at day 7 were identified by hypothesis testing using chi squared tests followed by multivariate logistic regression analysis. Factors with a p value less than 0.05 were considered significant. RESULTS: The participants were predominantly males 65.4% (68/104) and a third (36.5% (38/104)) were between 46 and 65 years. The prevalence of AKI among malaria patients at 48 hours was 26% (27/104). The prevalence of AKI among malaria patients at day 7 was 18.3% (19/104). On multivariate logistic regression, we found that factors that were significantly associated with AKI at 48 hours were male sex (OR 127, CI 3.4-4700, P = 0.008) and hemoglobin <7.5g/dl (OR 36.5, CI 1.7-797.7, P = 0.022), and factor associated with AKI at day 7 was baseline platelet count <25×103 per mm3 (OR 77.8 CI 1.045-5798.6, P = 0.048). Only two patients needed hemodialysis (1.9%) and there were no deaths. CONCLUSION: Acute kidney injury is a common complication in patient with falciparum malaria. When managed well it has an excellent prognosis and necessitates dialysis in only a minority of patients. Male sex and hemoglobin is associated with AKI at 48 hours and baseline platelet count is associated with AKI at 7 days.

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.

OBJECTIVE: The cause of the metabolic disturbances in sepsis remains uncertain, but there is increasing evidence suggesting that haemodynamic changes are not solely responsible. We addressed the question of whether endotoxin has a significant effect on cellular oxygen metabolism, independent of confounding haemodynamic defects. DESIGN: Prospective, controlled experimental study. SETTING: University Laboratory. MODEL: Human hepatocyte cell line. METHODS: The oxygen consumption rate (OCR) was calculated from the fall in oxygen tension in a sealed cuvette containing Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measured in control cells and after 1, 6 and 24 h of endotoxin exposure. In a second series of experiments, resting and maximal OCR was measured after 6 and 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respiratory chain from ATP synthesis, thereby removing negative feedback and allowing the respiratory chain to work at maximal rate. RESULTS: Endotoxin caused a rise in resting OCR at 1 h which was significant by 6 h but had returned to control values by 24 h. Maximal OCR also increased at 6 h, however exposure to endotoxin for 24 h significantly reduced maximal OCR compared to the control cells. CONCLUSIONS: Endotoxin has complex effects on cellular energy metabolism causing an initial rise in the oxygen consumption rate and a significant limitation in oxygen consumption capacity at 24 h. These complex effects would be in keeping with the varied responses seen in patients.

Iron depletion and anaemia: prevalence, consequences, diagnostic and therapeutic implications in a developing Pakistani population.

The prevalence of iron deficiency anaemia in Karachi, Pakistan, was examined in a group of 100 children, aged 2 to 6 years, and 200 adult females, aged 17 to 35 years. Anaemia, defined as a haemoglobin level less than 11.5 g/dl, was present in 47% of the children and 30% of the adult females. The majority of subjects had normal red cell counts and MCV, but haematocrit and MCH were below normal in one-quarter of the children and one-third of the adult females. More than half of both children and adult females had serum ferritin levels below normal. Many also had elevated iron binding capacity and reduced serum iron levels. Iron deficiency may be superimposed on folate deficiency in this population. The potentially serious consequences and higher prevalence of iron deficiency anaemia in children and women of childbearing age demand greater efforts toward diagnosis and eradication in developing countries.

PIP: Iron deficiency anemia has more serious consequences on the health of people in developing than developed nations. In Karachi Pakistan 300 subjects were examined to determine the prevalence of iron deficiency anemia: 100 children (49 males and 51 females) aged 2-6 years; 100 females aged 17-21 years with no history of pregnancy; and 100 females aged 25-35 with at least 1 prior pregnancy. Most subjects came from the lower to middle income groups, with only 10% from the higher income bracket. Blood samples were taken to measure serum ferratin, serum iron, total iron binding capacity (TIBC), red cell indices and films. Results showed that anemia was present in 47% of the children, a 30% of the adult females. More than half of both children and adult females had serum ferritin levels measuring below normal. Elevated iron binding capacity and reduced serum iron levels were found in many subjects. In the children, iron deficiency may be superimposed on folate deficiency. As a result, low levels of serum ferritin go hand in hand with iron depletion, and this is directly dependent upon the diet and socioeconomic conditions of the populace.

Platinum plus cyclophosphamide plus radiotherapy is superior to platinum alone in 'high-risk' epithelial ovarian cancer (residual negative and either stage I or II, grade 3, or stage III, any grade).

Patients with epithelial ovarian cancer (EOC) referred to our institution are stratified into risk groups based on their stage, grade and presence of residual cancer, with a specific treatment policy for each group. One-hundred and thirty-one patients with no visible residual tumor following primary surgery and either stage I, grade 3; stage II, grade 3; or stage III, any grade EOC were treated between November 1983 and the end of December 1991. Regimen A (cisplatin 75 mgm-2 and cyclophosphamide 600 mgm-2 intravenously every 4 weeks for 6 cycles with abdominopelvic irradiation between cycles 3 and 4) was used until April 1989 and was then replaced with Regimen B (cisplatin 75 mgm-2 intravenously every 3 weeks for 6 cycles). The 5-year actuarial overall and failure-free survivals were 78% and 64% respectively. Multivariate analysis identified increasing stage and treatment with Regimen B as independent adverse prognostic factors for failure-free survival. The importance of treatment regimen reached statistical significance for the stage I patients (P = 0.04) but not stage II (P = 0.11) or stage III (P = 0.79). It is possible to undertreat EOC as shown by the inferior results achieved with Regimen B (single agent cisplatin) compared to Regimen A (cisplatin-cyclophosphamide, irradiation). This effect of treatment regimen was particularly important for the lower-stage patients. Our postulate is that treatment resistant clones are less regularly present in lower-stage patients, and that a certain minimum amount of treatment is required to eliminate all the sensitive cancer.

'Moderate-risk' ovarian cancer (stage I, grade 2; stage II, grade 1 or 2) treated with cisplatin chemotherapy (single agent or combination) and pelvi-abdominal irradiation.

We placed patients with invasive epithelial ovarian cancer into four distinct prognostic groups: 'low', 'moderate', 'high' and 'extreme' risk. The 'moderate-risk' group contained all residual negative, stage I and II patients with two exceptions: stage Ia or b, grade 1 cancers and grade 3 cancers. They were treated with primary surgery, usually including bilateral salpingo-oophorectomy, hysterectomy and omentectomy. Chemotherapy was then given (cisplatin at 100 mg m-2 every 2 weeks for three cycles) followed by pelvi-abdominal irradiation (2250 cGy in 10 fractions to the pelvis and 2250 cGy in 22 fractions to the whole abdomen including pelvis). An early cohort with ascites or positive washings instead received six cycles of cisplatin and cyclophosphamide at 75 mg m-2 and 600 mg m-2 every 4 weeks with the same pelvi-abdominal irradiation sandwiched between cycles 3 and 4. One-hundred and nine patients were treated between November 1983 and December 1989. Median follow-up was 4.7 years (range 0.7-9 years). The 5-year actuarial overall and failure-free survivals were 81% and 76%, respectively. Chronic toxicity, although usually minor, included 15% with peripheral neuropathy or ototoxicity and 23% with chronic abdominal complaints. Our combined-modality results are similar to those obtained by other centers utilizing either pelvi-abdominal irradiation alone or cisplatin-based chemotherapy alone.

Carcinoma of cervix, the King Faisal Specialist Hospital & Research Center experience--the need for screening for cervical cancer in developing countries.

The King Faisal Specialist Hospital and Research Center opened in 1975 to provide specialized medical treatment to the citizens of Saudi Arabia and to promote prevention of disease through research and education. It is a national and middle eastern tertiary care hospital for oncology and a principle center for radiation therapy in Saudi Arabia. In this retrospective study, 504 patients with carcinoma of the cervix were analysed. Of the 504 patients, 410 received treatment with curative intent, which comprised radical surgery alone, radical radiation alone or combination surgery and radiation. The overall 3, 5 and 10 years survival of all 504 patients was 64%, 55% and 40%, respectively and for 410 patients treated with curative intent it was 74%, 61% and 51%, respectively. Multivariate analysis, using the Cox regression method, showed that the stage of the disease is the only significant prognostic factor influencing relapse-free survival. Stage for stage, treatment outcomes at King Faisal Specialist Hospital and Research Center match those achieved in the First world, but two-thirds of patients (rather than one-third) present with advanced disease at diagnosis. Therefore, any improvement in overall outcomes will require earlier diagnosis, achievable only through an effective screening program in the Kingdom of Saudi Arabia and similarly in the other Third world countries where patients present with advanced stage disease.

Laboratory diagnosis of iron deficiency in a developing country, Pakistan.

In developing countries, such as Pakistan, laboratories do not routinely screen for iron deficiency unless the patient presents with symptoms of anaemia. Efforts to prevent the often serious consequences of iron depletion are hampered in developing countries by the expense and impracticality of routinely screening patients using bone marrow examination. Assays for serum iron concentrations, total iron-binding capacity or haemoglobin and examinations of blood films, although more practical, cannot detect the earliest stages of iron deficiency. Serum ferritin appears to be a sensitive, early indicator of iron deficiency and can be easily and relatively inexpensively determined using an immunoassay kit. In the present study, serum ferritin levels were determined using immunoassay and compared to blood films, serum iron levels and total iron-binding capacity values in 300 apparently healthy Pakistanis. In the early stages of iron deficiency, serum ferritin appeared to be a sensitive measure of iron depletion.

Impact of introducing a sedation management guideline in intensive care.

To ensure that sedative agents in the intensive care unit are used for maximum benefit, a guideline that promotes the accurate and continuous assessment of patients' needs is indicated. This observational 24-month prospective study investigated the effect of introducing a sedation management guideline into a 10-bedded multidisciplinary intensive care unit on length of stay, severity of illness, mortality and the number of bed days provided. Costs for all sedative drugs were calculated as cost per bed day. Intensive care unit mortality remained constant before and after guideline introduction. The length of stay of non-cardiac surgery patients was mean (SD) 4.6 (4.4) and 5.1 (4.3) days, respectively (p = 0.2). Monthly sedative cost before guideline introduction was pound 6285 compared to pound 3629 afterwards (p< or =0.0001), representing a real saving of pound 63 759 in sedative costs over the 2 years following introduction of the guideline. Guideline-directed management for sedation significantly reduces the cost of sedative drugs per bed day without any negative effect on length of ICU stay and outcome.

The use of regional anaesthesia in patients at risk of acute compartment syndrome.

A delay in the diagnosis of an acute compartment syndrome can be devastating to the patient. The increasing use of regional anaesthesia in the management of orthopaedic and trauma patients raises concerns about the potential for delay in the diagnosis of acute compartment syndrome. We undertook a postal survey to assess the usage of regional anaesthesia in patients with lower limb fractures. The study showed that regional anaesthesia is being used in patients at risk of compartment syndrome and without compartment pressure monitoring equipment being available. The anaesthetists questioned had seen cases of acute compartment syndrome being masked by regional anaesthesia. We recommend that there is an urgent need to establish joint guidelines between the orthopaedic and anaesthetic communities on the usage of regional anaesthesia in patients with lower limb fractures to reduce further morbidity from delays in the diagnosis of compartment syndrome.

Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer.

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.

Internal mammary lymphoscintigraphy in breast carcinoma: possible significance in relation to current treatment.

A diagnostic modality to study parasternal lymph nodes was examined at the Cancer Control Agency of British Columbia, Vancouver. Forty-five patients with carcinoma of the breast were studied. The data correlate well with that from other centres in regard to anatomic validity, lymph node distribution, cross drainage and findings in relation to the stage of disease. The frequency of lymphoscintigraphic abnormalities was almost twice as high in relation to lesions situated in the centre and inner half of the breast as compared with outer half lesions. Twenty-eight per cent of patients demonstrated cross drainage between parasternal lymphatics. In 11% of the patients, nodes were situated at locations greater than 4 cm from the midline. Work is in progress to study the correlation of lymphoscintigraphy with disease in the nodes. The data indicate that this study can be used in other centres in the management of patients with mammary carcinoma.

Survey of use of end-tidal carbon dioxide for confirming tracheal tube placement in intensive care units in the UK.

The use of end-tidal carbon dioxide monitoring to confirm the correct placement of a tracheal tube immediately after intubation is mandatory in the operating theatre. Tracheal intubation in critically ill patients can be challenging. Quick and accurate confirmation of tracheal tube placement is essential to minimise complications. This survey explored the use of end-tidal carbon dioxide monitoring to confirm tracheal tube placement in intensive care units in the UK. Questionnaires were sent to either the lead clinician or clinical director of randomly selected general adult intensive care units. One hundred and twenty-seven replies were received from the 215 questionnaires sent (response rate 59%). Twenty per cent of the units did not have an end-tidal carbon dioxide monitor, 20% had one end-tidal carbon dioxide monitor per bed and 60% had one end-tidal carbon dioxide monitor between several beds. Only 50% of the units having an end-tidal carbon dioxide monitor use it to confirm correct tracheal tube placement. Of these 50%, only about a third use it for every intubation. Seventy-two per cent of respondents felt that end-tidal carbon dioxide is well suited to confirm correct placement of tracheal tube in critically ill patients, but 50% did not think that confirmation using end-tidal carbon dioxide should be mandatory for intubations outside the operating theatre. Half of the units not having end-tidal a carbon dioxide monitor cited lack of resources as a reason. In summary, although four in every five intensive care units surveyed have end-tidal carbon dioxide monitors, only a small proportion use them to confirm correct placement of tracheal tube after intubation.

A survey of pre-operative optimisation of high-risk surgical patients undergoing major elective surgery.

Pre-operative optimisation of high-risk patients undergoing major elective surgery has been shown to decrease peri-operative morbidity and mortality. It is also cost effective because of the resulting decrease in postoperative complications. A questionnaire was sent to 170 intensive care and high dependency units in Britain in order to quantify the number of units practising pre-operative optimisation. There was a 91% response rate. Of the respondents familiar with the evidence advocating pre-operative optimisation, 91% believe pre-operative optimisation improves outcome but only 62% admit patients for such preparation. Moreover, only eight units (6%) admit more than 25% of eligible patients. The reasons given for not admitting such patients pre-operatively are a lack of manpower, beds or both. This survey demonstrates the need for greater investment of resources into intensive care and high dependency units, so that clinicians can deliver high-quality evidence-based healthcare in accordance with the principles of clinical governance.

Acute pancreatitis as a model of sepsis.

Severe acute pancreatitis has many similarities to sepsis syndrome and septic shock. The haemodynamic features of cardiovascular instability, reduced ejection fraction and decreased systemic vascular resistance are indistinguishable in each of these conditions. In addition there are many striking similarities in the cytokine and inflammatory mediator profiles, suggesting that the haemodynamic abnormalities may result from the same pathogenic mechanisms, albeit as a result of different inflammatory stimuli. Although septic complications of severe acute pancreatitis do arise these are usually late features and in the early phase of a severe attack there is sterile pancreatic necrosis. Evidence suggests that the important cytokines in the development of complications and multiple organ failure in severe acute pancreatitis are tumour necrosis factor-alpha, interleukin-1, interleukin-6 and interleukin-8. In addition, endotoxin and other important inflammatory mediators including platelet activating factor and phospholipase A2 are implicated in the development of complications in both severe acute pancreatitis and sepsis. Patients with severe acute pancreatitis are not an entirely homogeneous group but in terms of pathogenesis and complications of their disease they have much more in common with each other than the patients who are collected under the unifying diagnosis of 'sepsis'. The similar clinical and biochemical features between severe acute pancreatitis and sepsis make the former an excellent model for studying the pathogenesis of the sepsis syndrome.

Survival from massive intraoperative pulmonary thromboembolism during orthotopic liver transplantation.

We report a case of massive pulmonary embolism occurring at the time of graft reperfusion in a patient undergoing orthotopic liver transplantation. The clinical diagnosis of pulmonary embolus was aided by on-table echocardiography. Cardiopulmonary bypass and surgical embolectomy prevented her death. We discuss the differential diagnosis, possible aetiology of pulmonary embolism in this context and subsequent management.