Pramipexole in patients with early Parkinson’s disease (PROUD): a randomised delayed-start trial.


In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson’s disease (PD).


Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30—79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson’s disease rating scale (UPDRS). This trial is registered with, number NCT00321854.


Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early pramipexole group and 61 patients in the delayed pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early pramipexole and 179 (84%) patients given delayed pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early pramipexole group and 17 (8%) in the delayed pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug.


By clinical and neuroimaging measures, pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6—9 months. The results do not support the hypothesis that pramipexole has disease-modifying effects.

Source: Lancet


Pulmonary hypertension in β thalassaemia.

Pulmonary hypertension is one of the leading causes of morbidity and mortality in patients with haemolytic disorders and is a frequent finding in echocardiographic screening of patients with β thalassaemia. Substantial progress has been made in understanding of the multifactorial pathophysiology of pulmonary hypertension in β thalassaemia. Haemolysis, reduced nitric oxide bioavailability, iron overload, and hypercoagulopathy are among the main pathogenetic mechanisms. Various disease-directed therapeutic methods, such as transfusion, chelation, and splenectomy, have important roles in the development of pulmonary hypertension in β thalassaemia. Studies investigating the prevalence of pulmonary hypertension in β thalassaemia are mostly based on echocardiographic findings, and are thus limited by the scarcity of information derived from right heart catheterisation. Invasive pulmonary haemodynamic data are needed to clarify the true prevalence of pulmonary hypertension in β thalassaemia, to better understand the underlying pathophysiology and risk factors, and to define the optimum therapy for this devastating complication.

Source: Lancet

The nuclear option for insulinomas.

Although insulinomas are rare tumours, they have fascinated clinicians for many years because of the variety in clinical presentation, close association between symptoms and biochemistry, and striking response to surgical cure. In a patient who is otherwise healthy, and in the absence of a history of diabetes mellitus, intermittent hypoglycaemia is usually attributable to inappropriate insulin activity.1 If other causes can be excluded—which is not always easy if, for example, patients are knowingly injecting insulin or taking drugs that stimulate insulin release—insulinoma should be seriously considered as a diagnosis. Diagnosis can be proven by confirmed hypoglycaemia in the presence of inappropriate insulin secretion; however, threshold criteria for measurements of glucose and insulin are somewhat controversial. Recent guidelines suggest that blood glucose concentrations should be lower than 3 mmol/L to be regarded as hypoglycaemia,1 but at the Churchill Hospital in Oxford, UK, we noted that this cutoff produced too many false positives and have reverted to a stricter threshold of 2·2 mmol/L. Equally, the inappropriate level of insulin in the presence of hypoglycaemia has been set at 3 mIU/L, but because insulin assays have become more specific, this crucial concentration of insulin has decreased. Indeed, we have reported a confirmed insulinoma in a patient with an insulin concentration of 2·7 mIU/L.2 As in other areas of endocrinology, improved assays have led to more difficult diagnostic decisions. However, a C-peptide concentration of more than 200 pmol/L is a useful and potentially robust determinant of inappropriate insulin secretion.


After the diagnosis of insulinoma has been made, localisation of the tumour is the biggest challenge. Most tumours are benign and small, with almost all less than 2 cm in maximum diameter, so identification can be problematic. Previously, surgeons would operate and trust that they could feel the tumour by direct palpation, but nowadays this technique is rarely practised (although intraoperative ultrasound is still used). CT scanning has good resolution but the difference in tissue density might not allow clear discrimination of the tumour. We reported that MRI was the most sensitive discriminatory imaging technique, identifying about 75% of tumours, and this sensitivity might be improved with diffusion-weighted imaging.3 Other groups have emphasised the role of endoscopic ultrasound.4 Intra-arterial injection of calcium with measurement of hepatic vein insulin is often used, but is invasive and only regionalises rather than localises the tumour; however, it can help confirm an anatomically identified abnormality.3—5 Thus, a need remains for precise localisation of these tumours. Nuclear medicine has been suggested to be useful in this context because it depends on functional aspects rather than simple anatomical size, but somatostatin scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) PET have not proved useful for these benign tumours.

In The Lancet Diabetes & Endocrinology, Emanuel Christ and colleagues6 ingeniously speculated that because most insulin cells contain receptors for incretins—specifically the glucagon-like peptide-1 receptor (GLP-1R)—injection of radiolabelled exendin-4, a GLP-1R agonist, might identify these tumours where other techniques have failed. Following on from an initial pilot study7 showing the feasibility of this technique, the group now report on 30 patients who were referred for exendin-4 scanning in centres in Switzerland, Germany, and the UK. All patients had either no lesion or only a suspicion of one on CT or MRI scanning, to exclude patients with evidence of malignant insulinoma. Christ and colleagues were able to report on 25 patients who had histological confirmation of insulinoma after surgery; of these, 23 had both CT/MRI and 111In-DTPA-exendin-4 scanning.6 CT/MRI correctly identified 47% (95% CI 27—68) of insulinomas in this study and endoscopic ultrasound correctly diagnosed seven of nine patients assessed using this technique. 111In-DTPA-exendin-4 scanning was 95% (75—100) sensitive, and was the only modality to correctly identify the tumour in all ten instances of histologically confirmed insulinoma where the other imaging was negative, although there were four false positives. Patients had a mean fall in blood glucose concentrations of 1·3 mmol/L (IQR 0·8—2·1) during the study so glucose infusions are required with the technique. Notably, the investigators used a different chelating agent, DPTA, in this study than in previous studies,7 which might cause fewer side effects (such as nausea and hypoglycaemia).

The radiotracer technique seems to be less effective for malignant tumours than benign tumours (radiolabelled octreotide might be more useful) and is not yet commercially available.8 However, it might allow for the identification of tumours not otherwise readily visualised, and should decrease the number of blind laparotomies, decreasing surgical morbidity, and could also allow for an increased rate of laparoscopic removal. Furthermore, some 5—10% of these tumours are a manifestation of multiple endocrine neoplasia type 1 (MEN1), in which multiple lesions frequently occur in the pancreas and identification of insulinomas is difficult. In Christ and colleagues’ study, two patients had MEN1 and their insulinomas were identified and successfully removed after 111In-DTPA-exendin-4 scanning.

A few points warrant emphasis. All patients in the study were selected for inclusion and had uncertain imaging, and at some point a direct comparison against optimum MRI and possibly endoscopic ultrasound and calcium-stimulated venous catheterisation should be done. At the moment, the new radiotracer technique is probably best reserved for those cases in which conventional localisation techniques have not worked. In time, PET isotopes might become available that are more sensitive and can reduce scan times (although whether this would work well for the pancreas is unknown). Endocrinologists should nevertheless regard the nuclear technique as offering great potential benefit to our patients in the future.

Source: Lancet

Food intake and childhood obesity: accurate estimation of requirements?

The first two decades of life are biologically unique because of the complex interaction between genes and environment driving, partly via hormones, the mature phenotype of an individual. During this time, body weight and composition change rapidly and are particularly sensitive to obesity-promoting factors. In The Lancet Diabetes & Endocrinology, Kevin Hall and colleagues1 present a model that allows for the simulation of body weight and energy balance dynamics in children and adolescents.

Their model showed that, contrary to common perception, the energy needed to accrue body weight in excess of that gained through normal growth is higher than the energy content of the extra mass accumulated. This finding is explained by the higher energy requirement associated with increased body weight. Higher fat-free mass increases basal energy requirements;2 higher body mass increases energy requirements for physical activity (ie, weight-bearing activities);3 and higher food intake (as a result of increased energy requirements accompanying weight gain) increases the energy used for digestion, absorption, and processing of food ingested (ie, meal-induced thermogenesis).4 Increased energy is also spent on synthesis of new tissue.5 Therefore, the requisite energy to gain extra weight rises as the amount of weight gained increases.6 All these factors reduce the positive energy balance, thereby decreasing the speed and intensity of energy-storing processes during the dynamic phase of obesity development.

Hall and colleagues’ model showed that the extra energy intake required for excess weight gain in children is higher than that required in adults, emphasising that, in general, the dynamic phase of excess weight gain in children results from a pronounced increase in energy intake with respect to energy requirements for healthy-weight, age-matched peers. This observation contrasts with those on which standard clinical practice is based and has important consequences. Obese children and adolescents usually report similar food intake to non-obese peers. However, the results of studies78 in which stable isotopes are used to measure total energy expenditure in normal life show that the food intake of overweight or obese children and adolescents is under-reported. Furthermore, the accuracy of parents’ awareness of children’s portion sizes and reporting of children’s food intake is only moderate.910 Reduced awareness of food intake in obese or preobese children and their parents is an important limiting factor in the modification of nutritional behaviour, and associated under-reporting of food intake adversely affects clinicians’ planning of adequate dietary strategies. This issue should be addressed with the family as a crucial target of behavioural intervention, because it is not plausible to expect diet adherence when awareness of portion size and daily food intake is low.

Another important simulated finding of Hall and colleagues’ model is the difference between sexes in terms of changes in body composition with weight loss at puberty. At puberty, fat-free mass increases much more in boys than in girls, and thus the energy requirements of boys increase more than those of girls. Thus, if energy intake is kept constant, overweight boys could reach a healthy body composition after maturation (ie, outgrow obesity). However, attainment of healthy body composition for overweight girls through maintenance of a constant energy intake is more difficult without weight loss. The practical implication of this finding is that dietary treatment of obese and preobese children at puberty should differ between sexes and be tailored to individual energy requirements.

Hall and coworkers’ results support more accurate assessment of energy intake and comparison of these estimates with energy requirements calculated specifically for each child. They also provide suggestions for public health strategies for the prevention and treatment of childhood obesity. In particular, their results suggest that the best time for intervention is before puberty, especially in females. The energy imbalance gap is different for universal prevention, prevention in at-risk individuals, and treatment of obesity. Hall and colleagues’ model might help to identify expected energy requirements and, by extension, to calculate the energy imbalance gap to target. However, to translate into practice these desired changes in energy balance, it will be necessary to increase families’ knowledge and awareness of energy content and composition of childrens’ diets by designing effective and sustainable educational programmes about nutrition.

Source: Lancet

Dysphagia in a young woman.

A 31-year-old woman presented to our clinic with a history of intermittent dysphagia to both solid and liquid food for several years. Her dysphagia increased in severity, and in recent months, was accompanied by frequent postprandial chest tightness, and vomiting. Physical examination and routine laboratory workup showed no obvious abnormalities. Oesophagogastroduodenoscopy ,showed an elongated pouch with a blind end originating from the mid-oesophagus. A demarcation was clearly seen between the epithelium in the pouch and the normal oesophageal mucosa. Upper gastrointestinal series .showed an 8·4×2·8 cm pouch stemming from the thoracic oesophagus. The tubular structure’s blind end did not connect with the distal oesophagus, suggesting an incomplete duplication of the oesophagus. CT of chest () also showed a tube-like lesion with internal air-fluid level. Video-assisted thoracic surgery was done to remove the duplication, resulting in improvement of her symptoms.


Oesophageal duplication is a rare congenital malformation and occurs in about one in 8200 livebirths. It can be categorised into cystic or tubular forms, with the cystic type accounting for nearly 90—95% of cases. Oesophageal duplication can cause recurrent dysphagia, hoarseness, vomiting, respiratory distress or even haematemesis. Most duplications are detected before 2 years of age; 25—35% of the duplications were first identified during adulthood. Surgical resections should be considered in symptomatic patients, and close follow-up is recommended for the asymptomatic individuals because malignancy can develop from the pouch.

Source: Lancet


The dangers of being born too small or too soon.

Birth is dangerous, especially for infants born too small or too soon. Although much is known about the mortality risk for such infants in high-income countries, little is known about the risk in poorer countries. In The Lancet, Joanne Katz and colleagues begin to fill in the gap on just how dangerous it is to be born too small or too soon in a low-income or middle-income country.1 The investigators analysed more than 2 million birth outcomes from resource-poor countries in Asia, Africa, and Latin America and calculated the regional risk of neonatal and post-neonatal mortality associated with being born preterm, small-for-gestational age (SGA), or both.

Using data from 20 cohorts in 13 countries, Katz and colleagues show that being born SGA increased the risk of neonatal mortality by two to five times across the three regions, but being born preterm (<37 completed weeks of gestation) raised the risk by six to 26 times. When children were born both SGA and preterm, neonatal mortality was ten to 39 times higher than in otherwise normal neonates. These findings provide the first solid estimates of the excess risk of dying for infants in these categories of births for countries where 135 million babies are born every year.

Katz and colleagues’ findings advance our knowledge by going beyond the use of low birthweight (<2500 g) as a means of identifying infants in danger. The low birthweight category includes both premature and growth-restricted infants. It excludes newborn babies heavier than 2500 g who might also be premature or have restricted growth and therefore still have an increased risk of dying. As a result of these findings, the sources of neonatal mortality are now better known in the regions studied and appropriate interventions to prevent early deaths can be developed.

Katz and colleagues are also the first to document the high proportion of Asian and African newborn babies (21% and 16%, respectively) who are SGA (defined as the lowest tenth percentile of the growth reference) but neither preterm nor low birthweight. In view of the surprisingly high proportion of such infants, it is disappointing that the authors did not provide the associated mortality risk. Term-SGA infants had about three times higher risk of death (across all regions) during the early and late neonatal as well as the postneonatal periods, but these included a high proportion of low-birthweight (LBW) infants. The investigators state that the large group of infants who are SGA but not preterm or LBW have a higher mortality risk than term, appropriate weight-for-gestational-age infants, but we are left to wonder: how much higher?

The high prevalence of term SGA births and their excess risk of death throughout infancy suggest that there is more to know about these babies than just their weight-for-gestational age. They could also be shorter, as documented in Guatemala,2where linear growth failure was detectable as early as 15 weeks of gestation, and infants tend to be born “short and round”.3 Infants of HIV-infected mothers on antiretroviral therapy in Haiti and Zambia were also born small, largely because of shortness at birth rather than thinness.45 There has been much discussion about the causes and consequences of proportional (ie, short and round) versus disproportional (long and thin) phenotypes of SGA babies, with some evidence that thin SGA babies are at higher risk of adverse outcomes.67 Elucidation of the differences in mortality risk among types of SGA infants will require datasets that include infant length at birth, but such data are rare.

Katz and colleagues’ findings present important methodological challenges. The investigators included cohorts on the basis of completeness and quality of their data. Nonetheless, in six of the cohorts, they imputed some birthweights because some data were missing or measured too late. Some of the variability in birthweight might have resulted from the 72 h observation window used (during which breastfed neonates can lose up to 10% of their weight8). Unfortunately, the preferred reference dataset for calculating birthweight-for-gestational age (the Alexander reference9) provides data at only the tenth percentile, so the authors used a different reference dataset to identify infants below the third percentile.10 Both references are from large US populations, with data obtained in 1972—76 and 1991, respectively. The appropriateness of these reference populations, especially for the cohorts from South Asia, is unknown and might be among the factors that account for the high proportions of SGA births seen. Again, not knowing the excess mortality associated with the SGA babies who were term and not LBW, we wonder whether the use of the tenth percentile of the Alexander reference put too many babies in this risk category.

The analysis presented by Katz and colleagues is a substantial contribution, and points the way to further advances. Most of the cohort studies included were not representative of the country where they were done, and the studies included in a given region were also not representative of that region—eg, the vast majority of data from Latin America was from Chile. More representative data are surely needed. Also, many low-income or middle-income countries are in eastern Europe and central Asia, regions not represented in these analyses. The scarcity of data from these regions, however, is because of a dearth of global resources and attention rather than a product of poor study design. We hope that this important study can serve as a catalyst for the development of stronger datasets that require fewer assumptions and include additional essential information, including length at birth.

Source: Lancet


Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.


Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally.


We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC).


34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112 027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45—49 years was 5·28% (95% CI 3·38—8·17%) in women and 5·41% (3·41—8·49%) in men, and at age 85—89 years, it was 18·38% (11·16—28·76%) in women and 18·83% (12·03—28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% [2·04—4·07%] at 45—49 years and 14·94% [9·58—22·56%] at 85—89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% [4·86—8·15%] of women aged 45—49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39—3·09) in HIC and 1·42 (1·25—1·62) in LMIC, followed by diabetes (1·88 [1·66—2·14] vs 1·47 [1·29—1·68]), hypertension (1·55 [1·42—1·71] vs 1·36 [1·24—1·50]), and hypercholesterolaemia (1·19 [1·07—1·33] vs 1·14 [1·03—1·25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC.


In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease.

Source: Lancet.


Effect of household and community interventions on the burden of tuberculosis in southern Africa: the ZAMSTAR community-randomised trial.


Southern Africa has had an unprecedented increase in the burden of tuberculosis, driven by the HIV epidemic. The Zambia, South Africa Tuberculosis and AIDS Reduction (ZAMSTAR) trial examined two public health interventions that aimed to reduce the burden of tuberculosis by facilitating either rapid sputum diagnosis or integrating tuberculosis and HIV services within the community.


ZAMSTAR was a community-randomised trial done in Zambia and the Western Cape province of South Africa. Two interventions, community-level enhanced tuberculosis case-finding (ECF) and household level tuberculosis—HIV care, were implemented between Aug 1, 2006, and July 31, 2009, and assessed in a 2×2 factorial design between Jan 9, 2010, and Dec 6, 2010. All communities had a strengthened tuberculosis—HIV programme implemented in participating health-care centres. 24 communities, selected according to population size and tuberculosis notification rate, were randomly allocated to one of four study groups using a randomisation schedule stratified by country and baseline prevalence of tuberculous infection: group 1 strengthened tuberculosis—HIV programme at the clinic alone; group 2, clinic plus ECF; group 3, clinic plus household intervention; and group 4, clinic plus ECF and household interventions. The primary outcome was the prevalence of culture-confirmed pulmonary tuberculosis in adults (≥18 years), defined as Mycobacterium tuberculosis isolated from one respiratory sample, measured 4 years after the start of interventions in a survey of 4000 randomly selected adults in each community in 2010. The secondary outcome was the incidence of tuberculous infection, measured using tuberculin skin testing in a cohort of schoolchildren, a median of 4 years after a baseline survey done before the start of interventions. This trial is registered, number ISRCTN36729271.


Prevalence of tuberculosis was evaluated in 64 463 individuals randomly selected from the 24 communities; 894 individuals had active tuberculosis. Averaging over the 24 communities, the geometric mean of tuberculosis prevalence was 832 per 100 000 population. The adjusted prevalence ratio for the comparison of ECF versus non-ECF intervention groups was 1·09 (95% CI 0·86—1·40) and of household versus non-household intervention groups was 0·82 (0·64—1·04). The incidence of tuberculous infection was measured in a cohort of 8809 children, followed up for a median of 4 years; the adjusted rate ratio for ECF versus non-ECF groups was 1·36 (95% CI 0·59—3·14) and for household versus non-household groups was 0·45 (0·20—1·05).


Although neither intervention led to a statistically significant reduction in tuberculosis, two independent indicators of burden provide some evidence of a reduction in tuberculosis among communities receiving the household intervention. By contrast the ECF intervention had no effect on either outcome.


We assessed prevalence of tuberculosis in 24 communities in Zambia and South Africa, after 3 years of ECF or household interventions for tuberculosis control. Of 64 463 randomly selected individuals, 894 individuals had active tuberculosis. Averaging over 24 communities the geometric mean of tuberculosis prevalence was 832 per 100 000 population. We also measured the incidence of tuberculous infection in a cohort of 8809 children, followed up for a median of 4 years. The adjusted prevalence ratio for prevalence and the adjusted rate ratio for incidence did not differ significantly for the ECF versus non-ECF or for the household versus non household groups. However, for the household versus non-household groups the upper bounds of the CI for both prevalence ratio and incidence rate ratio were close to unity. The concordance of two robust outcome measures, measured in different population groups and with different methods suggests that the household intervention did have some effect on the burden of tuberculosis in these communities.

The convergence of HIV and tuberculosis has led to an urgent need for an evidence-based public health response to reduce the burden of tuberculosis at the community level. Cluster-randomised trials should provide the gold standard for evidence-based policy making.

A systematic review of published work identified five studies that provided evidence for the effect of interventions on the epidemiology of tuberculosis at community level . Apart from preliminary data from the ZAMSTAR trial, two were randomised trials—the DETECTB trial of enhanced case-finding strategies in Zimbabwe and a trial of a household-level intervention in Brazil. The ZAMSTAR trial is the only study to measure the effect of public health interventions on tuberculosis with a randomised design and direct measurements of the burden of disease as the endpoint. The ZAMSTAR trial covered a population of almost 1 million people and was designed to detect reductions in prevalence of tuberculosis, and incidence of tuberculous infection, of 30%. Our study identified no evidence that the ECF intervention had an effect on the burden of tuberculosis at community level. However, despite not reaching statistical significance, there is plausible evidence that the household intervention did reduce the burden of tuberculosis in these communities.


Source: Lancet

Bill & Melinda Gates Foundation.

Noma: a neglected enigma.

Noma is a disease surrounded by riddles. It manifests itself only in the poorest populations in developing countries, enclosed by ignorance and extreme poverty. The worldwide prevalence of noma is unknown—estimates range from 30 000 to 140 000 cases.1 Most cases of noma worldwide occur in the so-called noma belt, which is situated directly south of the Sahara and runs across Africa from Senegal to Ethiopia. Another puzzle is that child mortality and malnutrition are prevalent on the Indian subcontinent, but noma is not reported there.23 The prevention and treatment of noma is not a priority in the countries where the disease is prevalent. Moreover, deaths from noma are not included in the mortality statistics of these countries. The cause of noma—the biological mechanism that ignites the gangrene—remains a mystery. Although the disease is clearly an opportunistic infection, we still do not know whether some of the commensal microorganisms in the oral microbiota play a particular part in the expanding gangrene. Also puzzling is how an unknown percentage (a common estimate suggests 10%) of noma patients survive the often extensive gangrene without any medical treatment. Antibiotic treatment of noma has not been subject to medical research, except for in some old observational studies.4 Furthermore, after one and a half centuries of surgical experiments, a good surgical treatment for a frequent sequela of noma, complete trismus of the mouth, has still not been found.5

The study by Baratti-Mayer and colleagues, undertaken in Niger, focuses on risk factors for noma. It is admirable that this large group of Swiss scientists, almost all members of the only scientific group on noma in the world, GESNOMA, has embarked on such a large and well-organised prospective, matched, case-control study to assess the risk factors for noma, and even more admirable that they have collected their data successfully under very difficult circumstances.

Their results confirm that malnutrition has a paramount role in the development of noma, and that poverty is associated with the disease. They also confirm a link between noma and recent illnesses of respiratory and intestinal origin. A new aspect to their study is the inventory of the oral microbiota in patients with noma and in controls. Their results do not confirm the role of Fusobacterium necrophorum (present in herbivores) as a trigger organism for noma, as suggested by Enwonwu and colleagues6 who hypothesised that the presence of herbivore livestock was a potential risk factor for noma. Baratti-Mayer and colleagues also describe differences in the intraoral microbiota of noma patients and controls, with a lower amount of Fusobacterium genus and spirochetes in patients with noma than in healthy controls. This result is intriguing because previous findings by Stewart,7 Eckstein,8 and Emslie9 showed the presence of spirilliform and fusiform microorganisms (called Borrelia vincenti and Fusiformis fusiformis at that time), often in large numbers, in biopsy samples taken from the transitional zone between the gangrene and healthy tissue, which suggested an important infiltrating role for these two microorganisms. In this context, the results of this study do not solve the puzzle of the trigger of this devastating gangrene but rather magnify it. Invasive diagnostics with, for example, needle biopsies from this transitional zone could help to elucidate the nature of this gangrene.

An interesting finding, which is not commented on in the Discussion section, is that all 82 patients with noma received amoxicillin and metronidazole, resulting in a mortality rate of 8·5%. This article is, as far as I know, the first publication reporting treatment results of a series of noma patients since 1966, when Michael Tempest reported a similar mortality rate of 8% in 250 patients treated with penicillin.4 This finding implies that a combination of amoxicillin and metronidazole is a good treatment to give to patients with noma, and perhaps also a penicillin, in view of the results of half a century ago.

However, a major problem is that most patients with noma worldwide do not have access to medical facilities because they are not available or are too expensive. Patients might consult a traditional healer, whose treatment (often a branding iron or caustic herbs) will lead to a deterioration in the patient’s condition. Western non-governmental organisations have also provided treatment in the past. Unfortunately, such programmes are now in jeopardy because of political instability and concomitant insecurity for aid workers from developed countries.

Noma is a disease that can be prevented completely by a particular level of economic welfare for the poorest people in society. This degree of welfare has been reached by most of the world’s population, which has expanded across the planet for thousands of years. An old companion on this journey of expansion, which is found on the edges of human being’s habitat (and is the case for every animal), is hunger and death. Death by starvation is expressed in many ways, of which noma is iconic as the “face of poverty”.10 We want to eradicate phenomena such as extreme poverty, famine, and starvation, as seen in the definition of the Millennium Development Goals and the recent G8 focus on nutrition. The future will show us whether or not these goals are the starting points of a feasible global health target.


1 Fieger A, Marck KW, Busch R, Schmidt A. An estimation of the incidence of noma in north-west Nigeria. Trop Med Int Health 2003; 8: 402-407. CrossRef | PubMed

2 Black RE, Cousens S, Johnson HL, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375: 1969-1987. Summary | Full Text | PDF(1713KB) | CrossRef | PubMed

3 Gragnolati M, Shekar M, Das Gupta M, Bredenkamp C, Lee Y. India’s undernourished children: a call for reform and action.World Bank, 2005. (accessed June 2, 2013).

4 Tempest MN. Cancrum oris. Br J Surg 1966; 53: 949-969. CrossRef | PubMed

5 Montandon D. Surgery of noma: a 20-year experience. Stomatologie 2007; 104: 1-9. PubMed

6 Falkler WA, Enwonwu CO, Idigbe EO. Isolation of Fusobacterium necrophorum from cancrum oris (noma). Am J Trop Med Hyg 1999; 60: 150-156. PubMed

7 Stewart MJ. Observations on the histopathology of cancrum oris. J Pathol 1912; 16: 221-225. PubMed

8 Eckstein A. Noma. Am J Dis Children 1940; 59: 219-237. PubMed

9 Emslie RD. Cancrum oris. Dent Pract Dent Rec 1963; 13: 481-495. PubMed

10 Marck KW. Noma, the face of poverty. Hannover: MIT-Verlag GmbH, 2003.

Source: Lancet

The Dangers of Using Plastic Water Bottles..

Bottled water in your car is very dangerous. People should not drink bottled water that has been left in a car. The heat reacts with the chemicals in the plastic of the bottle which releases dioxin into the water. Dioxin is a toxin increasingly found in breast cancer tissue. So please be careful and do not drink bottled water that has been left in a car.

Use a stainless steel canteen or a glass bottle instead of plastic.

This information is also being circulated at Walter Reed Army Medical Center … No plastic containers in microwaves. No plastic water bottles in freezers. No plastic wrap in microwaves.

Dioxin chemical causes cancer, especially breast cancer. Dioxins are highly poisonous to cells in our bodies. Don’t freeze plastic bottles with water in them as this releases dioxins from the plastic. Recently the Wellness Program Manager at Castle Hospital , was on a TV program to explain
this health hazard.

We should not be heating food in the microwave using plastic containers…..
This especially applies to foods that contain fat. The combination of fat, high heat and plastic releases dioxin into the food.

Instead use glass, such as Pyrex or ceramiccontainers for heating food… You get the same result, but without the dioxin.. So, such things as TV dinners, instant soups, etc., should be removed from
their containers and heated in something else.

Paper isn’t bad but you don’t know what is in the paper. It’s safer to
use tempered glass, such as Pyrex, etc.

A while ago some of the fast food restaurants moved away from the styrene foam containers to paper. The dioxin problem is one of the reasons….

Plastic wrap, such as Cling film, is just as dangerous when placed over foods to be cooked in the microwave. As the food is nuked, the high heat causes poisonous toxins to actually melt out of the plastic wrap and drip into the food. Cover food with a paper towel instead.

Source: Raw For Beauty