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author:("gaffar, S")
1.  Poverty, Food Insufficiency and HIV Infection and Sexual Behaviour among Young Rural Zimbabwean Women 
PLoS ONE  2015;10(1):e0115290.
Despite a recent decline, Zimbabwe still has the fifth highest adult HIV prevalence in the world at 14.7%; 56% of the population are currently living in extreme poverty.
Cross-sectional population-based survey of 18–22 year olds, conducted in 30 communities in south-eastern Zimbabwe in 2007.
To examine whether the risk of HIV infection among young rural Zimbabwean women is associated with socio-economic position and whether different socio-economic domains, including food sufficiency, might be associated with HIV risk in different ways.
Eligible participants completed a structured questionnaire and provided a finger-prick blood sample tested for antibodies to HIV and HSV-2. The relationship between poverty and HIV was explored for three socio-economic domains: ability to afford essential items; asset wealth; food sufficiency. Analyses were performed to examine whether these domains were associated with HIV infection or risk factors for infection among young women, and to explore which factors might mediate the relationship between poverty and HIV.
2593 eligible females participated in the survey and were included in the analyses. Overall HIV prevalence among these young females was 7.7% (95% CI: 6.7–8.7); HSV-2 prevalence was 11.2% (95% CI: 9.9–12.4). Lower socio-economic position was associated with lower educational attainment, earlier marriage, increased risk of depression and anxiety disorders and increased reporting of higher risk sexual behaviours such as earlier sexual debut, more and older sexual partners and transactional sex. Young women reporting insufficient food were at increased risk of HIV infection and HSV-2.
This study provides evidence from Zimbabwe that among young poor women, economic need and food insufficiency are associated with the adoption of unsafe behaviours. Targeted structural interventions that aim to tackle social and economic constraints including insufficient food should be developed and evaluated alongside behaviour and biomedical interventions, as a component of HIV prevention programming and policy.
PMCID: PMC4307980  PMID: 25625868
2.  Middle East respiratory syndrome coronavirus: epidemiology and disease control measures 
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection.
PMCID: PMC4226520  PMID: 25395865
MERS; Middle East respiratory syndrome coronavirus; epidemiology; control measures; transmission; Saudi Arabia
3.  Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin 
PLoS ONE  2014;9(9):e106517.
Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.
To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users.
One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m2) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes.
Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×103/µL vs 205.56 [123] ×103/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]).
Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.
PMCID: PMC4152258  PMID: 25181525
4.  A Quantitative Proteomic Approach to Identify Significantly Altered Protein Networks in the Serum of Patients with Lymphangioleiomyomatosis (LAM) 
PLoS ONE  2014;9(8):e105365.
Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition affecting approximately 3.4–7.5/million women, with an average lag time between symptom onset and diagnosis of upwards of 4 years. The aim of this work was to identify altered proteins in LAM serum which may be potential biomarkers of disease. Serum from LAM patient volunteers and healthy control volunteers were pooled and analysis carried out using quantitative 4-plex iTRAQ technology. Differentially expressed proteins were validated using ELISAs and pathway analysis was carried out using Ingenuity Pathway Analysis. Fourteen proteins were differentially expressed in LAM serum compared to control serum (p<0.05). Further screening validated the observed differences in extracellular matrix remodelling proteins including fibronectin (30% decrease in LAM, p = 0.03), von Willebrand Factor (40% reduction in LAM, p = 0.03) and Kallikrein III (25% increase in LAM, p = 0.03). Pathway networks elucidated the relationships between the ECM and cell trafficking in LAM. This study was the first to highlight an imbalance in networks important for remodelling in LAM, providing a set of novel potential biomarkers. These understandings may lead to a new effective treatment for LAM in the future.
PMCID: PMC4136818  PMID: 25133674
5.  Comparison of Paracetamol (Apotel®) and Morphine in Reducing Post Pure Head Trauma Headache 
This randomized, clinical trial evaluates the analgesic and safety of paracetamol and Morphine in management of headache.
This study aimed to evaluate the analgesic and safety effects of intravenous single dose of paracetamol, versus morphine in post trauma headache in emergency departments.
Patients and Methods:
This study was a single-center, prospective, randomized, double-blind clinical trial conducted on two groups treated with intravenous paracetamol and intravenous morphine. Thirty patients were enrolled in each group. Patients (18-55 years-old adults) complaining from headaches due to pure trauma were included in the study. The inclusion criteria required patients to have headachesof more than 40 mm on a 100 mm visual analogue scale without any pathological findings in their clinical examinations and imaging studies.
Mean duration required to treat the headache was 37.43 and 71.93 minutes in the groups administered paracetamol (group A) and morphine (group B), respectively. After 15 minutes of treatment, this changed to 31.7 ± 18.0 mm (95% CI 8.2 to 25.2) and 48.3 ± 14.1 mm (95% CI 8.2 to 25.2) in groups A and B, respectively. Headache of the patients of group A significantly mitigated in comparison with group B (P < 0.005). Headache of group Apatients was significantly mitigated 30 minutes after treatment (P < 0.005).
Intravenous paracetamol is an effective and safe treatment for patients admitted to the emergency department with headaches caused by head trauma.
PMCID: PMC4164985  PMID: 25237630
Post Trauma Headache; Paracetamol; Morphine
6.  Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island 
Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.
The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ≤85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms.
The mean DQ score was 86.3 (95%CI: 81.0–91.5) in infected children compared to 100.2 (95%CI: 98.0–102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45–5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <−2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children.
The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.
Author Summary
Chikungunya virus (CHIKV), an alphaviral infection transmitted by day-biting Aedes mosquitoes, is widespread in Asia and in Africa. Usually, CHIKV causes a self-limiting arthritide, except in debilitated people and in neonates, for whom it can lead to severe disease. Mother-to-child perinatal transmission of CHIKV is a rare event that can occur in the setting of large-scale outbreaks when the risk of maternal viremia at the term of pregnancy becomes non-negligible. In that event, CHIKV can give rise to neonatal infection with a probability of 50%, and prostration and encephalopathy, the two leading clinical pictures in the neonate, represent a continuum in the gradation of an undiscovered central nervous system involvement. We have followed-up 33 children infected at birth between June 2005 and April 2006 on the island of La Réunion, Indian Ocean, and 135 uninfected controls, for assessing their neurodevelopmental performance around the age of two years. Fifty-one percent of infected children had a global neurodevelopmental delay compared to 15% of uninfected peers. Multivariate analysis and neuroradiology suggest without irrefutable evidence a causal relationship between CHIKV infection and neurocognitive outcomes. Our findings suggest that CHIKV infection, acquired in the perinatal period, can cause severe disease with lifelong expected disability.
PMCID: PMC4102444  PMID: 25033077
7.  Defining the Role of the Academic Neurohospitalist in Residency Education 
The Neurohospitalist  2014;4(3):127-132.
We sought to better understand the potential impact of the burgeoning neurohospitalist model of inpatient care on education of neurology residents and to better define possible roles for “neurohospitalists” in residency education.
We designed a brief qualitative open-ended survey directed toward academic leaders in neurology and distributed it by e-mail to every academic neurology department in the United States and Canada.
Of 83 respondents, 36 (43%) had an active neurohospitalist program and only 10% felt certain they would not have 1 within the next 5 years. All respondents expected to have residents continue to be involved with inpatient care. The main perceived advantage for resident education associated with neurohospitalists was inpatient care expertise, and the main expected disadvantage was decreased exposure to subspecialty attendings. The majority anticipated positive impact on all Accreditation Council for Graduate Medical Education core competencies predominantly based on neurohospitalists’ expertise in the inpatient setting.
The majority of academic neurology departments are expected to have a neurohospitalist program within the next 5 years. There are several perceived advantages and disadvantages to such a program for education of neurology residents. In general, the impact of these programs is expected to improve resident education. Regardless of expectations, neurohospitalists will likely play a prominent role in the education of the next generation of neurologists.
PMCID: PMC4056419  PMID: 24982716
education; techniques; neurohospitalist; clinical specialty; quality
8.  Ameboma: an unusual cause of gastrointestinal bleeding during severe leptospirosis 
BMC Infectious Diseases  2014;14:299.
Severe leptospirosis occurs mainly in a tropical environment and includes icterus, acute renal failure and hemorrhages. These bleedings, which are mainly a consequence of acute homeostatic disturbances, can also reveal simultaneous diseases. Coinfections with other tropical diseases have been previously reported during leptospirosis. To our knowledge, invasive amebiasis, which can induce gastrointestinal bleedings, has never been described in the course of severe leptospirosis.
Case presentation
In this report, we describe a case of a 60 year-old man living in Reunion Island (Indian Ocean, France) admitted to our intensive care unit for severe Leptospira interrogans serovar icterohaemorrhagiae infection with neurological, renal, liver and hematological involvement. Two lower gastrointestinal bleedings occurred 7 and 15 days after admission. The first episode was promoted by hemostatic disturbances while the second bleeding occurred during low-dose heparin therapy. Colonoscopy revealed a pseudo-tumoral inflammatory mass of the recto-sigmoid junction. Histological examination found trophozoites inside mucinous exudate suggestive of Entamoeba histolytica. Amoebic serology was strongly positive whereas careful detection of cysts or trophozoites on saline-wet mount was negative in three consecutive samples of stools. Amoxicillin followed by metronidazole therapy, combined with supportive care, led to an improvement in the clinical and biological patient’s condition and endoscopic appearances.
Clinicians should be aware that gastrointestinal bleeding during severe leptospirosis could not solely be the consequences of hemostatic disturbances. Careful endoscopic evaluation that may reveal curable coinfections should also be considered.
PMCID: PMC4047549  PMID: 24894109
Leptospirosis; Weil’s disease acute renal failure; Amebiasis; Coinfection
9.  Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus 
The New England journal of medicine  2013;369(5):407-416.
In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care–acquired MERS-CoV infections.
Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced.
Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases).
Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
PMCID: PMC4029105  PMID: 23782161
10.  HIV Transmission at a Saudi Arabia Hemodialysis Unit 
This study confirms the occurrence of hemodialysis-associated HIV infection. The occurrence of such transmission is linked to the suboptimal compliance with prevention and control of infection measures.
Background. Hemodialysis is associated with increased risk of healthcare-associated infections but considered a low-risk setting for human immunodeficiency virus (HIV) transmission. We investigated 3 hemodialysis unit (HDU) patients with new HIV infections to determine whether transmission was hemodialysis-associated and to correct factors that contributed to transmission.
Methods. Each patient was evaluated for HIV risk factors. Blood samples were tested to determine relatedness of HIV strains. Clinical data (gathered over 18 months) was reviewed to identify seroconversions at 12 HDUs. Infection prevention and control practices were evaluated at 14 HDUs.
Findings. No other HIV seroconversions were identified during the study. HIV gag, pol, and env gene sequences were consistent with a clonal relationship. HIV and hepatitis C virus prevalence rates at one HDU 1 (5.7% and 6.5%, respectively) were higher than for 11 other HDUs (0% and 0.15%, respectively).
Conclusions. Sequencing supports either patient-to-patient or common-source transmission. Infections occurred despite Saudi Arabia's low HIV prevalence and national dialysis policies that emphasize stringent infection prevention and control practices.
PMCID: PMC4144264  PMID: 24846636
hemodialysis; healthcare-associated infections; epidemic outbreak; HIV; HCV
11.  Pharmacognostic studies of stem, roots and leaves of Malva parviflora L. 
To establish quality control parameters of a locally occurring medicinal plant, Malva parviflora which is utilized as folk medicine in Sialkot area in Pakistan.
In pharmacognostic studies different types of evaluations were carried out that focus on microscopic, macroscopic, fluorescence analysis and organoleptic evaluations.
The distinguishing characters of stem were the presence of parenchyma, cork cells, irregular shape calcium oxalate crystals, simple and compound starch granules and fusiform fibers with pits. Root microscopic characters were presence of simple and spherical starch granules with rounded or slit hilum, groups of lignified xylem fibers, reticulate vessels, and sieve tissues. Leaves microscopy indicated the presence of paracytic stomata, lignified fibers having pits, spiral and annular vessels, numerous sclereids while in fruit microscopy epicarp, thin walled cells endocarp, thin walled parenchyma and collenchyma of mesocarp and abundant thick walled endospermic cells containing aleurone grains and micro rosette crystals. Macroscopic study of leaves showed, 5-7 lobed reniform-shape, glabrous-surface, reticulate-venation in the leaves. Macroscopic features of roots showed type of root-taproot, surface-glabrous and stem was 1-10 dm tall simple to branched and may be prostrate or ascending. Similarly fruit was of schizocarp type.
This study provides the scientific data for the proper identification and establishment of standards for the use of Malva parviflora.
PMCID: PMC3985058  PMID: 25182728
Malva parviflora; Stomatal index; Palisade ratio; Chloral hydrate; Evaluation; Transverse section
12.  Age at diagnosis of female breast cancer in Oman: Issues and implications 
South Asian Journal of Cancer  2014;3(2):101-106.
Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age.
Aim and Objective:
The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer.
Materials and Methods:
All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data.
A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population.
BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to be further studied and validated. This phenomenon of BC in younger age may have significant implications and effects ranging from screening, diagnosis, management, prognosis, and cost of treatment.
The impact on young women diagnosed with BC is enormous, ranging from psychosocial to healthcare services and economics. There is a need to study it further in depth in developing World.
PMCID: PMC4014639  PMID: 24818104
Breast cancer; breast cancer in Oman; young age; young breast cancer
13.  Bacteremic skin and soft tissue infection caused by Prevotella loescheii 
BMC Infectious Diseases  2014;14:162.
Anaerobes are a major component of gut flora. They play an important role in the pathogenesis of infections resulting from breaches in mucus membranes. Because of the difficulties in cultivating and identifying it, their role continues to be undermined. The purpose of this paper is to report a case of Prevotella loescheii bacteremic skin and soft tissue infection and review the literature.
Case presentation
A 42-year-old Caucasian man was admitted for an elective bariatric surgery. A lengthy intensive care unit stay and buttocks decubitus ulcers complicated his post-operative course. After being transferred to a long-term care facility, the decubitus ulcer became secondarily infected with multiple bacteria including P. loescheii; an anaerobe that grew in blood and wound cultures. The patient was treated successfully with aggressive surgical debridement, antibiotics and subsequent wound care.
P. loescheii colonizes the gut and plays an important role in periodontal infections. In rare occasions and under suitable circumstances, it can infect skin and soft tissues as well as joints. Given the difficulties in isolating anaerobes in the microbiology lab, considering this bacterium alongside other anaerobes in infections of devitalized tissue is indicated even if cultures were reported negative.
PMCID: PMC3997918  PMID: 24661318
Anaerobe; Bacteremia; Prevotella loescheii
14.  A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity 
BMC Medical Genetics  2014;15:25.
A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder.
Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer.
DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*).
Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals.
PMCID: PMC3941482  PMID: 24571530
Ichthyosis; Phenotypic variability; ELOVL4; Non-sense mutation
15.  Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus 
mBio  2014;5(1):e01062-13.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1.
MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.
PMCID: PMC3944817  PMID: 24549846
16.  Controversies and considerations regarding the termination of pregnancy for Foetal Anomalies in Islam 
BMC Medical Ethics  2014;15:10.
Approximately one-fourth of all the inhabitants on earth are Muslims. Due to unprecedented migration, physicians are often confronted with cultures other than their own that adhere to different pdigms.
In Islam, and most religions, abortion is forbidden. Islam is considerably liberal concerning abortion, which is dependent on (i) the threat of harm to mothers, (ii) the status of the pregnancy before or after ensoulment (on the 120th day of gestation), and (iii) the presence of foetal anomalies that are incompatible with life. Considerable variation in religious edicts exists, but most Islamic scholars agree that the termination of a pregnancy for foetal anomalies is allowed before ensoulment, after which abortion becomes totally forbidden, even in the presence of foetal abnormalities; the exception being a risk to the mother’s life or confirmed intrauterine death.
The authors urge Muslim law makers to also consider abortion post ensoulment if it is certain that the malformed foetus will decease soon after birth or will be severely malformed and physically and mentally incapacitated after birth to avoid substantial hardship that may continue for years for mothers and family members. The authors recommend that an institutional committee governed and monitored by a national committee make decisions pertaining to abortion to ensure that ethics are preserved and mistakes are prevented. Anomalous foetuses must be detected at the earliest possible time to enable an appropriate medical intervention prior to the 120th day.
PMCID: PMC3943453  PMID: 24499356
Abortion; Ensoulment; Islam; Glorious Qur’an; Termination of pregnancy; TOP
17.  Estimation with Cox models: cause-specific survival analysis with misclassified cause of failure 
Epidemiology (Cambridge, Mass.)  2012;23(2):194-202.
While epidemiologic and clinical research often aims to analyze predictors of specific endpoints, time-to-the-specific-event analysis can be hampered by problems with cause ascertainment. Under typical assumptions of competing risks analysis (and missing-data settings), we correct the cause-specific proportional hazards analysis when information on the reliability of diagnosis is available. Our method avoids bias in effect estimates at low cost in variance, thus offering a perspective for better-informed decision-making. The ratio of different cause-specific hazards can be estimated flexibly for this purpose. It thus complements an all-cause analysis. In a sensitivity analysis, this approach can reveal the likely extent and direction of the bias of a standard cause-specific analysis when the diagnosis is suspect. These two uses are illustrated in a randomized vaccine trial and an epidemiologic cohort study respectively.
PMCID: PMC3903130  PMID: 22317803
18.  Spontaneous bilateral peripapillary, subhyaloid and vitreous hemorrhage with only minor platelet deficit in idiopathic thrombocytopenic purpura 
A 45-year-old female with underlying idiopathic thrombocytopenic purpura (ITP) complained of acute onset of reduced vision and floaters, in both eyes, for 3 weeks. Visual acuity was 6/36 and 6/60 in the right eye and left eye, respectively. Ophthalmoscopy showed bilateral peripapillary, subhyaloid and vitreous hemorrhage. Hematological evaluation revealed moderate anemia (hemoglobin: 93 g/L) and mild thrombocytopenia (platelets: 120×109/L). She was co-managed by a hematologist and ophthalmologists; she was treated medically. Follow-up care during the next 6 weeks revealed spontaneous, partially resolving hemorrhage, with improvement of visual acuity. The purpose of this case report is to highlight ophthalmic involvement of ITP in this patient, despite her only-mild thrombocytopenia, and her spontaneous recovery, despite her receiving only medical treatment.
PMCID: PMC3908908  PMID: 24493935
idiopathic thrombocytopenic purpura; subhyaloid hemorrhage; vitreous hemorrhage
19.  Variability of the QuantiFERON®-TB Gold In-Tube Test Using Automated and Manual Methods 
PLoS ONE  2014;9(1):e86721.
The QuantiFERON®-TB Gold In-Tube test (QFT-GIT) detects Mycobacterium tuberculosis (Mtb) infection by measuring release of interferon gamma (IFN-γ) when T-cells (in heparinized whole blood) are stimulated with specific Mtb antigens. The amount of IFN-γ is determined by enzyme-linked immunosorbent assay (ELISA). Automation of the ELISA method may reduce variability. To assess the impact of ELISA automation, we compared QFT-GIT results and variability when ELISAs were performed manually and with automation.
Blood was collected into two sets of QFT-GIT tubes and processed at the same time. For each set, IFN-γ was measured in automated and manual ELISAs. Variability in interpretations and IFN-γ measurements was assessed between automated (A1 vs. A2) and manual (M1 vs. M2) ELISAs. Variability in IFN-γ measurements was also assessed on separate groups stratified by the mean of the four ELISAs.
Subjects (N = 146) had two automated and two manual ELISAs completed. Overall, interpretations were discordant for 16 (11%) subjects. Excluding one subject with indeterminate results, 7 (4.8%) subjects had discordant automated interpretations and 10 (6.9%) subjects had discordant manual interpretations (p = 0.17). Quantitative variability was not uniform; within-subject variability was greater with higher IFN-γ measurements and with manual ELISAs. For subjects with mean TB Responses ±0.25 IU/mL of the 0.35 IU/mL cutoff, the within-subject standard deviation for two manual tests was 0.27 (CI95 = 0.22–0.37) IU/mL vs. 0.09 (CI95 = 0.07–0.12) IU/mL for two automated tests.
QFT-GIT ELISA automation may reduce variability near the test cutoff. Methodological differences should be considered when interpreting and using IFN-γ release assays (IGRAs).
PMCID: PMC3900587  PMID: 24466211
21.  Human Leptospirosis on Reunion Island: Past and Current Burden 
Since 1953, leptospirosis has been recognized as a public health problem on Reunion Island. In 2004, was implemented a specific surveillance system that included systematic reporting and the realization of environmental investigations around hospitalized cases. Here, we present the synthesis of historical data and the assessment of 9 years of leptospirosis surveillance. From 2004 to 2012, 414 hospitalized cases were reported. Cases of leptospirosis occurred mostly during the rainy season from December to May. Approximately 41% of infections occurred at home, 12% of infections occurred during aquatic leisure and 5% of cases were linked to professional activities. Furthermore, for 41% of cases, the place of infection could not be determined due to the accumulation of residential and non-residential exposure. Most of the cases of leptospirosis were linked to rural areas or traditional, rural occupations. We did not observe a shift to recreational leptospirosis as described in some developed countries. According to the new surveillance system, the number of reported cases has regularly increased since 2004. This situation is in part due to the improvement of the system in the first years but also to a real increase in the number of detected cases due to the introduction of molecular methods and to increased biological investigation into the Dengue-like syndrome by medical practitioners on the island since the Chikungunya crisis in 2006. This increase is probably due to surveillance and diagnosis biases but need to be carefully monitored. Nevertheless, the possibility of an outbreak is always present due to climatic events, such as after the “hyacinth” hurricane in 1980.
PMCID: PMC3924485  PMID: 24434593
leptospirosis; epidemiology; surveillance; human; Reunion Island; Indian Ocean
22.  The Role of Esophageal Stent Placement in the Management of Postesophagectomy Anastomotic Leak 
Anastomotic leak after esophagectomy is one of the most challenging complications resulting in a high morbidity and mortality and prolonged hospitalization. The study intended to assess the outcome of endoluminal self-expanding stent in the treatment of this problem.
Settings and Design:
Department of Thoracic and Cardiovascular Surgery, Arhus University Hospital, Skejby, Arhus, Denmark. A retrospective study.
Patients and Methods:
From January 2007 to December 2010, 209 patients underwent esophagectomy for malignant disease of the esophagus or the cardia. Twenty patients developed anastomotic leak. Treatment consisted of conservative measures, surgery, and stent placement. Details of treatment, clinical outcome, complications, and mortality were evaluated.
Statistical analysis:
One hundred and forty-seven patients (70.3%) had carcinoma of the cardia, whereas 62 patients (29.7%) had esophageal carcinoma. Twenty patients (9.5%) developed anastomotic leak; small (<1 cm) in two patients (10%); managed conservatively and bigger than 1 cm in 15 patients (75%); treated with an esophageal stent (Hanaro stent, DIAGMED Healthcare, Thirsk, YO7 3TD, United Kingdom). In three patients (15%), perforation of the staple line of the intrathoracic gastric conduit was found and managed by reoperation. Functional sealing of anastomoses after stent placement could be achieved in 10 patients (67%). Stent-related morbidity developed in five patients (33%): Migration of the stent, n=3 and tracheoesophageal fistula, n=2. Stents were smoothly removed 3 weeks after discharge. The mean hospital stay was 25 days. There was only one stent-related death (6.6%).
Endoluminal stent implantation is an effective and safe option in the management of postesophagectomy leaks.
PMCID: PMC3952418  PMID: 24496156
Anastomosis; esophagus; endoscopy
23.  Comprehensive Healthcare module: medical and pharmacy students’ shared learning experiences 
Medical Education Online  2014;19:10.3402/meo.v19.25605.
The Comprehensive Healthcare (CHC) module was developed to introduce pre-clinical medical and pharmacy students to the concept of comprehensive healthcare. This study aims to explore their shared learning experiences within this module.
During this module, medical and pharmacy students conducted visits to patients’ homes and to related community-based organisations in small groups. They were required to write a reflective journal on their experiences regarding working with other professions as part of their module assessment. Highly scored reflective journals written by students from the 2011/2012 academic session were selected for analysis. Their shared learning experiences were identified via thematic analysis. We also analysed students’ feedback regarding the module.
Analysis of 25 selected reflective journals revealed several important themes: ‘Understanding of impact of illness and its relation to holistic care’, ‘Awareness of the role of various healthcare professions’ and ‘Generic or soft skills for inter-professional collaboration’. Although the primary objective of the module was to expose students to comprehensive healthcare, the students learnt skills required for future collaborative practice from their experiences.
The CHC module provided early clinical exposure to community-based health issues and incorporated some elements of inter-professional education. The students learnt about the roles of other healthcare professions and acquired soft skills required for future collaborative practice during this module.
PMCID: PMC4202196  PMID: 25327980
education; medical; undergraduate; inter-professional education; comprehensive healthcare; primary healthcare
24.  Identical Strength of the T Cell Responses against E2, nsP1 and Capsid CHIKV Proteins in Recovered and Chronic Patients after the Epidemics of 2005-2006 in La Reunion Island 
PLoS ONE  2013;8(12):e84695.
To characterize the immunity developed by patients infected by chikungunya virus (CHIKV), we studied the intensity and specificity of CHIKV-specific T cells mediated responses in chronic and recovered patients at 12 to 24 months post-infection. T cells were challenged in vitro against CHIKV synthetic peptides covering the length of three viral proteins, capsid, E2 and nsP1 proteins as well as all inactivated virus particles. Cytokine production was assessed by ELISPOT and intracellular labeling. T cells producing IFN-γ were detected against CHIKV in 85% patient’s cells either by direct ELISPOT assay (69% of patients) or after expansion of memory T cells allowing the detection of both CD4 and CD8 specific-T cells in 16% additional cases. The IFN-γ response was mainly engaged in response to nsP1 or E2 (52% and 46% cases, respectively) but in only 27% cases against the capsid. The anti-E2 response represented half the magnitude of the total CHIKV IFN-γ production and was mainly directed against the C-terminal half part of the protein. Almost all patients had conserved a T cell specific response against CHIKV with a clear hierarchy of T cell responses (CD8 > CD4) engaged against E2 > nsP1 > capsid. More importantly, the intensity of responses was not significantly different between recovered and chronic patients. These findings constitute key elements to a better understanding of patient T cell immunoreactivity against CHIKV and argue against a possible defect of T cell immunoresponse in the chronicity post-CHIKV infection.
PMCID: PMC3871564  PMID: 24376836
25.  Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study 
Lancet  2013;382(9909):1993-2002.
Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.
Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done.
Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction.
We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed.
Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.
PMCID: PMC3898949  PMID: 24055451

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