Precise Pediatric Cancer Diagnosis Using Immunohistochemistry: Reducing Cost of Care and Improving Outcomes in a Low and Middle-Income Setting.

Childhood cancer is a significant cause of morbidity and mortality worldwide. It is the second-leading cause of non-communicable deaths among children worldwide with more than 90% of childhood cancer-associated mortality occurring in low-income and middle-income countries. Disparity in mortality rates has been linked to late presentation, inaccurate diagnosis, treatment abandonment and poor access to appropriate therapy. Access to enhanced diagnostics such as immunohistochemistry (IHC) is vital for proper diagnosis and prompt institution of appropriate treatment for children with cancers. However, despite the ever-increasing insight into the use of these techniques for timely and accurate diagnosis of pediatric cancers; simple histological diagnosis remains the mainstay in most of the LMIC owing to financial constraints, unavailability of facilities and skilled manpower. Limited access results in imprecise diagnosis including missed diagnosis, misdiagnosis, and wrong diagnosis, subsequently resulting in increased cost of care and poor treatment outcomes. This article focuses on the benefits of precise diagnosis among children who presented with cancers in an LMIC and the observed reduction in the cost of care, length of hospital stay, and improved outcome in the observed cohort as well as how to improve and promote access.

Le cancer infantile est une cause significative de morbidité et de mortalité dans le monde. Il s'agit de la deuxième cause de décès non transmissible chez les enfants dans le monde, avec plus de 90 % de la mortalité associée au cancer infantile survenant dans les pays à revenu faible et intermédiaire. La disparité des taux de mortalité a été associée à une présentation tardive, un diagnostic inexact, l'abandon du traitement et un accès insuffisant à une thérapie appropriée. L'accès à des diagnostics améliorés tels que l'immunohistochimie (IHC) est essentiel pour un diagnostic précis et la mise en place rapide d'un traitement approprié pour les enfants atteints de cancers. Cependant, malgré les connaissances de plus en plus approfondies sur l'utilisation de ces techniques pour un diagnostic rapide et précis des cancers pédiatriques, le diagnostic histologique simple reste le pilier dans la plupart des pays à revenu faible et intermédiaire en raison de contraintes financières, de l'indisponibilité des installations et du manque de personnel qualifié. Un accès limité se traduit par un diagnostic imprécis, notamment des diagnostics manqués, des erreurs de diagnostic et des diagnostics erronés, entraînant par la suite une augmentation du coût des soins et de mauvais résultats thérapeutiques. Cet article met l'accent sur les avantages d'un diagnostic précis chez les enfants présentant des cancers dans un pays à revenu faible et intermédiaire, et sur la réduction observée du coût des soins, de la durée du séjour à l'hôpital, ainsi que sur l'amélioration des résultats dans la cohorte observée, ainsi que sur la manière d'améliorer et de promouvoir l'accès. MOTS-CLÉS: Pédiatrie, enfants, Immunohistochimie, Cancer.

Psychometric properties of Drug Attitude Inventory among patients with schizophrenia.

Background: The treatment of patients diagnosed with schizophrenia has remained three-fold physical (pharmacological), psychological and social. Furthermore, the need to monitor adherence to the physical aspect of treatment has been a major concern to mental health practitioners as this usually affects the success of psychological and social treatment. Aim: My study aimed to determine the psychometric properties of Drug Attitude Inventory (DAI) among patients with schizophrenia. The study was carried out at the Neuropsychiatric Hospital, Aro Abeokuta Ogun State and on an average, about 150 patients were seen daily at the outpatient clinic. Methods: Internal consistency, item-total correlation (the two-way mixed method with absolute agreement) and Cronbach's alpha were evaluated using an intra-class correlation coefficient (ICC). This instrument's level of adequacy was determined using factor analysis (principal component analysis with varimax rotation). Result: Marital status and level of education were significantly associated with adherence. The Cronbach's alpha was 0.56 and principal components factor analysis with varimax rotation produced a three-factor solution. Conclusion: My study has shown that the DAI is a valid and reliable instrument and can be used in a clinical setting where there are limitations with time such as the outpatient clinic.

Job satisfaction, personality traits, and its impact on motivation among mental health workers.

Background: Working in a resource setting that caters to people's poor mental health is associated with increased vulnerability to physical, psychological, and social stressors that make motivation to work a difficult goal to attain. One way of viewing physical and social stressors in the workplace is to evaluate job satisfaction which has both intrinsic and extrinsic components. The personality of workers is a component of psychological wellbeing and this determines the way events and situations are perceived. Thus, the achievement of the mission and vision of an organisation will be dependent on the level of motivation of the employees which will be influenced by their predominant personality traits and the level of satisfaction at work. Aim: My study aimed to sought to highlight the relationship between motivation, job satisfaction and personality dimensions. Setting: The Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria. Methods: Our study involved a cross-sectional study of staff showing the relationship between motivation, job satisfaction and personality traits among mental health workers. A total of 146 participants using systematic proportional sampling were analysed with a response rate of 67.3%. A Socio-demographic Questionnaire, Minnesota Satisfaction Questionnaire (Short Version), Big Five Inventory and the Multidimensional Work-Motivation Scale were administered to the participants. In the analysis, linear correlation and linear regression were used to determine the relationship between continuous variables (Normality was determined using kurtosis and skewness) while t-test was used to determine the relationship between categorical independent variables and continuous dependent variables. Results: The level of significance was set at < 0.05 while higher scores using the Multidimensional Work-Motivation Scale represented motivated participants and vis-a-vis. The socio-demographic variable was explored using descriptive statistics; the relationship between personality, job satisfaction and motivation were explored using t-test. Most of the participants were married (80.8%), female (60.3%), with at least tertiary education (63%) and with an occupational status of class I (76%). The mean age of the participants was 40.29 ± 8.27 with a mean length of service of 13.63 ± 8.49. The most dominant personality traits were agreeableness (97.3%) and conscientiousness (97.3%), and the least was neuroticism (55.5). High agreeableness (0.01), high conscientiousness (0.03), and high openness (0.01) were significant and positively correlated with motivation. The relationship between motivation and gender (t = 4.26; p ≤ 0.001) and occupational status were statistically significant (t = -3.59; p ≤ 0.001). Conclusion: To proffer a solution to poor motivation in the workplace, human resource department should give more focus to individuals with high scores in agreeableness, conscientiousness, and openness. This is because it appears that they are more likely to be motivated at work and likely to move the organisation to a greater height. Besides, those with high neurotic scores who have already been employed will require some form of psychological remodelling (therapy), so they can contribute meaningfully to the institution.

Depression and quality of life among pregnant women in first and third trimesters in Abeokuta: A comparative study.

Background: Pregnancy is a dynamic time during which a woman's emotional state may undergo extensive change. There have been conflicting views about the magnitude of emotional turmoil that occurs during pregnancy. Some investigators suggest that pregnancy is a time of particularly good psychological adjustment; others have reported high levels of psychological challenge. Aim: Our study aimed to compare the prevalence and correlates of depression in the first and third trimesters of pregnancy and to determine the relationship between quality of life and depressive disorder. Setting: The antenatal clinic of the State Hospital, Ijaiye. Method: A descriptive, comparative study of depressive disorder and the quality of life between first- and third-trimester pregnant women (confirmed through a pregnancy test and an abdominopelvic ultrasound). Result: For each trimester, 285 participants were recruited. The prevalence of depression among the pregnant women who participated in the study was 7.2%. In the first trimester of pregnancy, the prevalence of depression was 30 (10.5%), while it was 11 (3.9%) in the third trimester of pregnancy. Collectively, the relationship between depression and QoL was significant in the overall domain, satisfaction with general health domain (t = 2.27; p = 0.03), psychological domain (t = 2.74; p = 0.010, and environmental domain (t = 4.57; p ≤ 0.01). Conclusion: Our study also highlights the need to pay closer attention to the psychological well-being and quality of life of all pregnant women and not just on their physical health and the baby's well-being.

Upregulation of Uric Acid Production and Caspase 3 Signalling Mediates Rohypnol-Induced Cardiorenal Damage.

The global prevalence of illicit drug use is on the increase with attendant complications like cardiorenal collapse. One such substance of abuse is rohypnol. Despite its ban in most countries, it remains a popular substance of abuse. Whether or not rohypnol induces cardiorenal injury and the associated mechanism is yet to be elucidated. Therefore, the present study investigated the effect of rohypnol on cardiorenal integrity and functions, and glucolipid metabolism. Forty-eight male Wistar rats randomized into six groups (n = 8/group) received (per os) vehicle, low-dose (2 mg/kg) and high-dose (4 mg/kg) rohypnol once daily for twenty eight days, with or without a cessation period. Data revealed that rohypnol exposure irreversibly caused insulin resistance, hyperglycaemia, and dyslipidaemia. This was accompanied by reduced cardiorenal mass and impaired cardiorenal cytoarchitecture and function. Furthermore, rohypnol treatment promoted oxidative stress, inflammation, genotoxicity, and decreased cardiorenal activities of Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase. These alterations were associated with enhanced uric acid generation and caspase 3 activity in the cardiorenal complex. Thus, this study reveals that rohypnol exposure triggers cardiorenal toxicity with incident insulin resistance, glucolipid and cardiorenal proton pump dysregulation, altered redox state, and inflammation via enhancement of uric acid generation and caspase 3-dependent mechanism.

Psychometric evaluation of personal evaluation of transitions in treatment amongst patients with schizophrenia.

BACKGROUND: Monitoring the antipsychotic medication adherence of outpatients with schizophrenia has focused majorly on the medication construct of adherence, whilst neglecting its psychosocial construct. AIM: The aim of this study was to provide the psychometric properties of personal evaluation of transitions in treatment (PETiT). SETTING: This study was conducted at the Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria. METHODS: This is a study of diagnostic accuracy of patients with a diagnosis of schizophrenia. Calculation of the sample size and oversampling was calculated as proposed by Cochrane. RESULTS: The Cronbach's α in this study at baseline was 0.82. Intra-class correlation coefficient was 0.81 (p ≤ 0.001). Medication construct was loaded into two factors or components whilst the psychosocial construct was loaded into four factors. CONCLUSION: The data depicted here indicated a successful validation and presentation of psychometric properties of PETiT which is self-administered, user friendly, psychometrically sound and sensitive to changes associated with treatment over time.

Mathematical modelling and optimal cost-effective control of COVID-19 transmission dynamics.

The novel coronavirus disease (COVID-19) caused by a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the current global health challenge. In this paper, an epidemic model based on system of ordinary differential equations is formulated by taking into account the transmission routes from symptomatic, asymptomatic and hospitalized individuals. The model is fitted to the corresponding cumulative number of hospitalized individuals (active cases) reported by the Nigeria Centre for Disease Control (NCDC), and parameterized using the least squares method. The basic reproduction number which measures the potential spread of COVID-19 in the population is computed using the next generation operator method. Further, Lyapunov function is constructed to investigate the stability of the model around a disease-free equilibrium point. It is shown that the model has a globally asymptotically stable disease-free equilibrium if the basic reproduction number of the novel coronavirus transmission is less than one. Sensitivities of the model to changes in parameters are explored, and safe regions at certain threshold values of the parameters are derived. It is revealed further that the basic reproduction number can be brought to a value less than one in Nigeria, if the current effective transmission rate of the disease can be reduced by 50%. Otherwise, the number of active cases may get up to 2.5% of the total estimated population. In addition, two time-dependent control variables, namely preventive and management measures, are considered to mitigate the damaging effects of the disease using Pontryagin's maximum principle. The most cost-effective control measure is determined through cost-effectiveness analysis. Numerical simulations of the overall system are implemented in MatLab ® for demonstration of the theoretical results.

Evaluation of Pantoea eucalypti FBS135 for pine (Pinus massoniana) growth promotion and its genome analysis.

AIMS: Pinus massoniana is one of the most widely distributed forest plants in China. In this study, we isolated a bacterial endophyte (designated FBS135) from apical buds and needles of P. massoniana. Investigations were performed to understand the effects of the strain on pine growth, its genomic features and the functions of the plasmids it carries. METHODS AND RESULTS: Based on its morphological features and 16S rRNA sequence, strain FBS135 was primarily identified as Pantoea eucalypti. We found that FBS135 not only promoted the growth of P. massoniana seedlings, but also significantly increased the survival rate of pine seedlings. The whole genome of FBS135 was sequenced, which revealed that the bacterium carries one chromosome and four plasmids. Its chromosome is 4 023 751 bp in size and contains dozens of genes involved in plant symbiosis. Curing one of the four plasmids, pPant1, resulted in a decrease in the size of the FBS135 colonies and the loss of the ability to synthesize yellow pigment, indicating that this plasmid may be very important for FBS135. CONCLUSIONS: Pantoea eucalypti FBS135 has a genomic basis to be implicated in plant-associated lifestyle and was established to have the capability to promote pine growth. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report that such a bacterial species, P. eucalypti, was isolated from pine trees and evidenced to have pine beneficial activities. Our results elucidate the ecological effects of endophytes on forest plants as well as endophyte-plant interaction mechanisms.

Psychoactive substance use among outpatients with severe mental illness: A comparative study.

BACKGROUND: Despite several studies on the prevalence and pattern of substance use in Nigeria, there is little information on substance use in patients diagnosed with serious mental illness (SMI) such as schizophrenia and bipolar affective disorder (BD). AIM: The aim of the study was to compare the pattern of psychoactive substance use among outpatients with BD and schizophrenia. SETTING: The study was conducted in a neuropsychiatric hospital in Nigeria. METHODS: Seventy five consecutive patients with a MINI-PLUS diagnosis of BD were compared with an equal number of patients obtained by systematic random sampling with a MINI-PLUS diagnosis of schizophrenia. RESULTS: The respondents with schizophrenia were aged 18-59 years (37.2 ± 9.99) and were predominantly young adult (49, 65.3%), men (46, 61.3%), who were never married (38, 50.7%). Overall, lifetime drug use prevalence was 52%, while for current use, overall prevalence was 21.3%. Participants with BD were aged 18-63 years (36.7 ± 10.29) and were predominantly young adult (53, 70.7%), women (44, 58.7%), who were married (32, 42.7%), with tertiary education (31, 41.3%). Overall, lifetime drug use prevalence was 46.7%, while current overall prevalence was 17.3%. These rates (lifetime and current) for both diagnostic groups are higher than what was reported by the World Health Organization in the global status report of 2014 (0% - 16%). The statistically significant difference between the two diagnostic groups was related to their sociodemographic and clinical variables and psychoactive substance use. CONCLUSION: Psychoactive substance use remains a burden in the care of patients diagnosed with schizophrenia and BD. Future policies should incorporate routine screening for substance use at the outpatient department with a view to stemming the tide of this menace.

Psychoactive substance use among outpatients with severe mental illness: A comparative study

Background: Despite several studies on the prevalence and pattern of substance use in Nigeria, there is little information on substance use in patients diagnosed with serious mental illness (SMI) such as schizophrenia and bipolar affective disorder (BD).Aim: The aim of the study was to compare the pattern of psychoactive substance use among outpatients with BD and schizophrenia.Setting: The study was conducted in a neuropsychiatric hospital in Nigeria.Methods: Seventy five consecutive patients with a MINI-PLUS diagnosis of BD were compared with an equal number of patients obtained by systematic random sampling with a MINI-PLUS diagnosis of schizophrenia. Results: The respondents with schizophrenia were aged 18­59 years (37.2 ± 9.99) and were predominantly young adult (49, 65.3%), men (46, 61.3%), who were never married (38, 50.7%). Overall, lifetime drug use prevalence was 52%, while for current use, overall prevalence was 21.3%. Participants with BD were aged 18­63 years (36.7 ± 10.29) and were predominantly young adult (53, 70.7%), women (44, 58.7%), who were married (32, 42.7%), with tertiary education (31, 41.3%). Overall, lifetime drug use prevalence was 46.7%, while current overall prevalence was 17.3%. These rates (lifetime and current) for both diagnostic groups are higher than what was reported by the World Health Organization in the global status report of 2014 (0% ­ 16%). The statistically significant difference between the two diagnostic groups was related to their sociodemographic and clinical variables and psychoactive substance use.Conclusion: Psychoactive substance use remains a burden in the care of patients diagnosed with schizophrenia and BD. Future policies should incorporate routine screening for substance use at the outpatient department with a view to stemming the tide of this menace

Mixed connective tissue disease complicated by heart failure in Ile-Ife, Nigeria: management challenges in a resource-limited economy.

BACKGROUND: Mixed connective tissue disease (MCTD; also known as Sharp's syndrome) is a rare autoimmune inflammatory disorder characterized by high titer of U1 ribonucleoprotein (U1RNP) antibody and clinical and serological overlap of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis is based on clinical and serological factors in criteria such as Alarcon-Segovia, Khan, Kusakawa, and Sharps. Cardiac disease can be a complication of connective tissue disease (CTD). There are few reports in Africa. AIMS: To present MCTD as underlying cause of heart failure with reduced ejection fraction and highlight challenges of investigations and treatment. OBJECTIVES: To highlight the first case in our center and discuss the cardiac, respiratory, and rheumatologic management. PATIENT AND METHODS: We present a 52-year-old woman with 3 weeks history of productive cough with whitish sputum, severe dyspnea, orthopnea, paroxysmal nocturnal dyspnea, right sided abdominal pain, leg swellings, a one year history of recurrent fever, Raynaud's phenomenon, small joint swellings and deformities with pain in both hands. RESULTS: On examination there was microstomia, tethered forehead and lower eyelid skin, tender swelling of the interphalangeal joints and arthritis mutilans. Laboratory findings showed estimated glomerular filtration rate <60 mL/kg/min/1.73 m2, U1RNP antibody levels were eight times upper limit of normal, elevated rheumatoid factor, speckled antinuclear antibody pattern, negative anticentromere antibody, anti Scl-70 and anticyclic citrullinated peptide. Chest X-ray/CT revealed pulmonary fibrosis. Echocardiography findings showed reduced ejection fraction of 40%, elevated pulmonary arterial pressure at rest of 60.16 mmHg. The patient showed improvement on antifailure drugs, but prednisolone was stopped for sudden reversal of previously controlled stage 2 hypertension (HTN), and the patient was discharged in a stable condition. Difficulties ensued in obtaining prompt definite results due to the unavailability of serologic tests in the hospital, and the tests were done outside the state and country. CONCLUSION: Identifying MCTD is critical, especially in patients requiring steroids that may worsen systemic HTN and heart failure. There is a need to have definitive investigative facilities for such patients in hospitals.

A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels.

STUDY QUESTION: Could drugs targeting ATP-sensitive K(+) (K(ATP)) channels prevent any spontaneous increase in intracellular Ca(2+) that may occur in human metaphase II (MII) oocytes under in vitro conditions? SUMMARY ANSWER: Pinacidil, a K(ATP) channel opener, and glibenclamide, a K(ATP) channel blocker, prevent a spontaneous increase in intracellular Ca(2+) in human MII oocytes. WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca(2+) homeostasis is crucial for cell wellbeing and increased intracellular Ca(2+) levels is a well-established indicator of cell stress. STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca(2+) levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP. PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean ± SD) age 34.1 ± 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca(2+)-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca(2+) monitoring was 80.4 ± 2.1 h. MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca(2+) increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 ± 11.8 AU (AU = arbitrary units; n = 23) to 91.8 ± 14.0 AU (n = 19; P < 0.001) after 2 h of monitoring. Pinacidil (100 µM) inhibited this increase in Ca(2+) (85.3 ± 12.3 AU at the beginning of the experiment, 81.7 ± 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 µM) also inhibited the increase in Ca(2+) (74.7 ± 10.6 AU at the beginning and 71.8 ± 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca(2+) that was inhibited by glibenclamide (100 µM; n = 9) but not by pinacidil (100 µM; n = 5). LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca(2+) in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 ± 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca(2+) homeostasis and, furthermore, the altered Ca(2+) homeostasis might have been associated solely with the protracted incubation. WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca(2+), which can be counteracted by drugs targeting K(ATP) channels. As Ca(2+) homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that K(ATP) channel openers and blockers should be tested as drugs for improving success rates of ART. STUDY FUNDING/COMPETING INTERESTS: University of Dundee, MRC (MR/K013343/1, MR/012492/1), NHS Tayside. Funding NHS fellowship (Dr Sarah Martins da Silva), NHS Scotland. The authors declare no conflicts of interest.

Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity.

STUDY QUESTION: Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER: We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY: For >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION: This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 µM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests. PARTICIPANTS/MATERIALS, SETTING, METHODS: All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of ≥ 60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P ≤ 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P ≤ 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased drug discovery screening approach including the examination of clinical samples, 3/43 compounds were identified as promising candidates for further study. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study and caution must be taken when extrapolating the results. Data for patients were from one assessment and thus the robustness of responses needs to be established. The n values for ICSI samples were relatively small. WIDER IMPLICATIONS OF THE FINDINGS: We have systematically screened and identified several compounds that have robust and effective stimulation (i.e. functional significance with longevity and no toxicity) of total and progressive motility under clinical conditions of treatment. These compounds could be clinical candidates with possibilities in terms of assisted reproductive technology options for current or future patients affected by asthenozoospermia or oligoasthenozoospermia. STUDY FUNDING/COMPETING INTERESTS: This study was funded primarily by the MRC (DPFS) but with additional funding from the Wellcome Trust, Tenovus (Scotland), University of Dundee, NHS Tayside and Scottish Enterprise. The authors have no competing interests. A patent (#WO2013054111A1) has been published containing some of the information presented in this manuscript.

Trust in primary care providers and antiretroviral adherence in an urban HIV clinic.

Interpersonal trust is an integral component of the patient-provider relationship and has been associated with patient adherence to medications. Studies suggest African Americans may have lower levels of trust in their health care providers than non-Hispanic Whites. This study examines the association between trust in one's primary care provider (PCP) and antiretroviral (ARV) adherence among 175 patients at an urban HIV clinic. Interviews elicited participants' level of trust in their current PCP using a multiple-item trust scale and assessed ARV adherence with a seven-day recall questionnaire. Logistic regression was used to ascertain the effect of trust in PCP on ARV adherence. High trust in PCP was significantly associated with increased odds of ARV adherence compared with low trust (adjusted odds ratio, 2.67; 95% confidence interval, 1.24 to 5.76; p=.01). Enhancing trust in PCPs may be a good target for interventions to improve ARV adherence, particularly among African American patients.

Prolonged febrile illness due to CTX-M-15 extended-spectrum ß-lactamase-producing Klebsiella pneumoniae infection in Nigeria.

We report on an 8-year-old patient with septicaemia unresponsive to therapy for five weeks. Undetected, extended-spectrum ß-lactamase (ESBL) production by the infecting Klebsiella strain was regarded as responsible for treatment failure. Intravenously administered imipenem during the sixth week led to sustained resolution of fever. Resource-limited hospitals can incur prohibitive costs from ESBL-producer infections because of diagnostic limitations and consequent treatment failure involving prolonged supportive therapy.

Effects of continuity of care and patient dispositional factors on the physician-patient relationship.

BACKGROUND: We developed a questionnaire to examine the influence of physician and patient variables on the quality of the physician-patient relationship. METHODS: More than 300 family medicine patients completed self-report measures of the physician-patient relationship and variables likely to influence it. RESULTS: The quality of relationship was related to continuity of physician care (having a primary physician, duration of that relationship, and frequency of visits) and to patient dispositional variables (neuroticism, positive and negative affectivity) but not to demographic variables. The regression model included having a primary physician, duration of relationship with that physician, and positive affectivity. Relationship quality was, in turn, associated with outcomes (adherence to care, treatment response, satisfaction with care, and commitment to physician). CONCLUSIONS: The quality of physician-patient relationship is influenced by physician continuity and patient dispositional variables. Better understanding of these may contribute to the therapeutic potential of this important relationship.

A prospective audit of the quality of documentation of gynaecological operations.

There is a paucity of audits in the speciality of Obstetrics and Gynaecology to estimate the standard of documentation of operation notes. Evidence from several audits across all specialities indicates the overall standard of reporting and documentation in medicine is poor, with many reports failing to contain important and pertinent data. Various attempts have been made to address these shortcomings. To estimate the degree of non-compliance in gynaecological practice, we set out to prospectively audit the standard of documentation of operation notes in a busy District General Hospital serving the largest Borough in terms of population in the city of London. An initial prospective audit was carried out in July 2008; and this was re-audited after 12 months using a standardised proforma based on the Royal College of Surgeons of England guidelines. There was evidence of significant improvement with the use of a standardised proforma.

Prevalence and Correlates of Physical Disability and Functional Limitation among Elderly Rural Population in Nigeria.

Background. The number of people surviving into old age is increasing, and it has now become a global phenomenon. Studies on the prevalence and correlates of physical disability and functional limitation among elderly Nigerians are scanty. Methodology. This is a community-based cross-sectional study conducted in 3 local government areas (LGAs) in Nigeria, using a multistage sampling technique. Functional limitations of 1824 elderly persons were tested using Tinetti performance-oriented mobility assessment tool (TPOMAT) and self-reported activities of daily living (ADL). ADL disability of ten, six, and five basic items were compared. Results. The prevalence ratios (PRs) of physical disability using the ten, six, and five basic ADL items were 28.3 (95% CI 25.2-31. 5), 15.7 (95% CI 13.4-19.8), and 12.1 (95% CI 9.8-15.3), respectively, while functional limitation was 22.5 (95% CI 18.1-24.4). Increased risk of disability was independently associated with female gender PR 3.6 (95% CI 1.5-7.4), advanced age ≥75 years; PR 22.2 (95% CI 14.5, 36.8), arthritis PR 3.7 (95% CI 2.6-4.6), stroke PR 4.8 (95% CI 3.7-7.9) and diabetes PR 6.1 (95% CI 4.3-7.1). Conclusions. The findings from this study are pointers to unmet needs of the elderly disabled Nigerians.

Hypochondriacal symptoms associated with a less therapeutic physician-patient relationship.

The purpose of this study was to examine the association between hypochondriacal symptoms and the physician-patient relationship. Family medicine patients (n = 310) completed self-report measures of hypochondriacal symptoms, quality of physician-patient relationship, and variables likely to influence that relationship. These variables included physician relationship factors, such as duration of relationship and frequency of visits, as well as patient characteristics, such as neuroticism and positive and negative affectivity. Hypochondriacal symptoms were negatively correlated (r = -.24) with the quality of physician-patient relationship. In addition to hypochondriacal symptoms, the regression model included having a primary physician, length of relationship with that physician, frequency of physician visits, and the level of positive affectivity in the patient. Hypochondriacal symptoms appear to be associated with a less therapeutic physician-patient relationship. Physicians must recognize symptoms of this kind in order to properly address the relationship needs of their patients.

Antimicrobial resistance in Escherichia coli strains from urinary tract infections.

BACKGROUND: An increase in resistance against many different drugs among urinary tract infection (UTI) E coli isolates has been observed in the last 2 decades. This study determined the trends of antimicrobial resistance in E coli to commonly used antibiotics. METHODS: The study was conducted in Ile-Ife, southwest Nigeria. Patients with features suggestive of UTI were investigated for presence of significant bacteriuria. Urine isolates were identified. Antimicrobial susceptibility was evaluated in accordance with standard bacteriological methods. RESULTS: Of 442 urine specimens, 158 (35.8%) yielded significant growth, including 41 (25.6%) with E coli. Among the E coil isolates, antimicrobial susceptibility varied in prevalence by agent in descending order as follows: nitrofurantoin (80%), ofloxacin (24%), ciprofloxacin (15%), nalidixic acid (10%), cotrimoxazole (5%), and amoxicillin/clavulanic acid (2%). No isolate was susceptible to amoxicillin, gentamicin, or tetracycline. All were also found to be resistant to at least 3 commonly used drugs. All 25 isolates tested for extended-spectrum beta-lactamase (ESBC) production were found to be presumptive ESBCs producers. CONCLUSION: The results demonstrate the continued susceptibility of E coil to nitrofurantoin and their widespread and increasing resistance to amoxicillin, gentamicin, cotrimoxazole, ciprofloxacin, ofloxacin, and tetracycline. Nitrofurantoin is a--and, in this locale, perhaps the only--rational drug for empiric treatment of uncomplicated UTI. There is a need for a comprehensive study of the involvement of ESBC-producing E coli in UTI in this environment.