Transforming Parkinson's Care in Africa (TraPCAf): protocol for a multimethodology National Institute for Health and Care Research Global Health Research Group project.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent. METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator. DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1ß was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1ß and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1ß were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Maternal deaths in rural Gambia.

The objective of this study was to determine causes and contributing factors to maternal deaths in a poor rural setting. We included all maternal deaths (N =42), identified from January to September 2002, in a remote area of The Gambia. To gain a comprehensive picture of medical causes and contributing factors a combination of audit procedure and verbal autopsy was applied. The results showed that anaemia (n =12) was the leading cause of death followed by haemorrhage (n =10), eclampsia (n =8) and obstructed labour (n =8). Placental abruption accounted for 9 of the 10 haemorrhage cases. Substandard obstetric care was identified for the majority of deaths. Substantial inadequacies were revealed at the hospital, characterized by operational difficulties and an uncoordinated emergency preparedness, including malfunction of the blood transfusion service, failure to obtain operative delivery, poor birth monitoring and lack of trained personnel, electricity, medical equipment and drugs. Substandard primary care and logistic difficulties within the referral process further complicated the situation. Delay in seeking care by the cases themselves played a less important role. It was concluded that interventions, addressing the profound deficiencies within the health care system and increasing access to emergency obstetric care, are warranted to reduce maternal deaths in a poor setting such as rural Gambia.

Monitoring mosquito net coverage for malaria control in Africa: possession vs. use by children under 5 years.

OBJECTIVES: To investigate the strengths and weaknesses of the indicators 'proportion of households possessing mosquito net(s)' and 'proportion of children under 5 years of age who slept under a net the preceding night' for monitoring malaria control. METHODS: Review of data from household surveys including demographic and health surveys in sub-Saharan African countries. RESULTS: Net possession ranged among 14 surveyed regions from 0.1% to 28.5% for insecticide-treated nets (ITNs) and among 69 regions from 3.6% to 79.7% for any net. Reported use during the preceding night by children under 5 years of age was between 0% and 16% for ITNs and between 0.7% and 74.5% for any net. On average, in households owning ITN(s), 55% of children slept under it (R2 = 0.97, P < 0.001). For any net, use was -4.2% + 0.875 x possession (R2 = 0.89, P < 0.001); the use of nets, however, also varied somewhat among the surveyed countries (P = 0.003). In-depth surveys suggested that use was lower than possession because: (i). nets were scarce (mean 1.8 per possessing household); (ii). nets were not always used for children and (iii). use was lower during hot, dry months than during cool rainy months, and many surveys had been conducted in the dry season. CONCLUSIONS: Not all mosquito nets owned by African households are being used for young children. Household education on the consistent use of nets for this vulnerable group is called for in malaria control programmes. Regular, district-level rapid assessments of household possession of nets should complement ongoing in-depth surveys. Data on 'use during the preceding night' must be interpreted taking the survey season into account.

Requirement of a centrosomal activity for cell cycle progression through G1 into S phase.

Centrosomes were microsurgically removed from BSC-1 African green monkey kidney cells before the completion of S phase. Karyoplasts (acentrosomal cells) entered and completed mitosis. However, postmitotic karyoplasts arrested before S phase, whereas adjacent control cells divided repeatedly. Postmitotic karyoplasts assembled a microtubule-organizing center containing gamma-tubulin and pericentrin, but did not regenerate centrioles. These observations reveal the existence of an activity associated with core centrosomal structures-distinct from elements of the microtubule-organizing center-that is required for the somatic cell cycle to progress through G1 into S phase. Once the cell is in S phase, these core structures are not needed for the G2-M phase transition.

Ultrasound detection of posterior scleral bowing in young patients with choroidal melanoma.

BACKGROUND: In evaluating young patients with choroidal melanomas, which are uncommon in people less than 30 years old, we noted that some had the ultrasound appearance of posterior scleral bowing. The purpose of this study was to determine the incidence of posterior scleral bowing in young patients with choroidal melanoma. METHODS: We reviewed the ultrasonograms of 24 patients less than 30 years of age (mean age 25 years [standard deviation (SD) 4.7 years]) who presented to an ocular oncology service in Toronto between May 1984 and May 1997. In all cases the diagnosis was choroidal melanoma. Histologic specimens were available in six cases. RESULTS: Scleral indentation posterior to the normal curvature of the globe was identified in 14 patients (58%). These patients had a mean tumour height of 4.4 mm (SD 2.0 mm) and mean tumour diameter of 9.5 mm (SD 2.9 mm). In the 10 patients with no scleral bowing the mean tumour height was 5.7 mm (SD 3.1 mm) and mean tumour diameter 11.5 mm (SD 3.8 mm). Pathological study (results available in nine cases in the scleral bowing group and four cases in the group without bowing) showed that all the tumours in the former group and three of those in the latter group were of the more indolent cell types, either mixed with predominantly spindle cells, or spindle cell. The six patients with histologic specimens were all in the scleral bowing group. The histologic features supported the ultrasound finding of posterior scleral bowing. No transscleral invasion occurred over the tumour region. INTERPRETATION: Posterior bowing of the sclera at the tumour site was observed in over half of young patients with choroidal melanoma. This phenomenon can be detected by ultrasonography and has a different appearance from that of choroidal excavation.

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.

Optimization of combined CT pulmonary angiography with lower extremity CT venography.

OBJECTIVE: We wanted to determine the time delay for maximum enhancement of the deep venous system of the lower extremities after standard CT pulmonary angiography. SUBJECTS AND METHODS: In 20 patients who had undergone standard CT pulmonary angiography, we measured arterial and venous enhancement at the level of the greater trochanter. These measurements were obtained at 30-sec intervals immediately after completion of CT pulmonary angiography. Ten measurements were obtained in 5 min. Time-density curves were plotted. RESULTS: We found that the median and average peak venous enhancements were 92 and 95 H, respectively. Time to peak enhancement was variable. Because of the broad shape of the venous time-density curve, near peak enhancement could be achieved in most patients at 2 min after CT pulmonary angiography. CONCLUSION: CT of the deep venous system of the lower extremities after standard CT pulmonary angiography, performed with appropriate timing considerations, allows near maximal enhancement of the venous system in most patients without altering the optimum CT pulmonary angiography protocol.

The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.

During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77% of nets were treated with insecticide. In contrast, in villages where charges were made coverage was only 14%. During the first year of the NIBP, mortality in children was significantly lower in villages where insecticide was provided free than in the control villages. Introduction of a charge for insecticide into the first group of villages and the provision of free insecticide in the latter abolished this difference. The cash income of rural Gambians is very limited and payment of even $2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia.

PIP: Insecticide for the treatment of bednets was provided free of charge to half of Gambia's primary health care (PHC) villages during the first year of the Gambian National Impregnated Bednet Program (NIBP). A high level of coverage was obtained and overall mortality among children aged 1-9 years was reduced 25% in villages where insecticide was provided. During the second year of the program, charges for insecticide of $0.50 per net were introduced to the 221 PHC villages which had previously received free insecticide, while the remaining PHC villages received free insecticide. In villages where insecticide was provided free during year 2, 77% of nets were treated with insecticide, far higher than the 14% coverage achieved in villages where fees were charged. During the first year of the NIBP, mortality in children was significantly lower in villages where insecticide was provided free compared to that in the control villages. Introducing a charge for insecticide in the first group of villages and providing free insecticide in the latter abolished that difference. Additional education on the benefits of net treatment and/or the provision of cheaper insecticide will be needed before the full benefits of net treatment can be fully realized in the Gambia.

Implementing a nationwide insecticide-impregnated bednet programme in The Gambia.

Earlier studies in The Gambia suggested that the use of impregnated bednets might prove to be a useful malaria control strategy. Based on the results of these studies, in 1992 the Government of The Gambia was encouraged to initiate a National Impregnated Bednet Programme (NIBP) as part of the National Malaria Control Programme Strategy. This paper describes the implementation process/procedure of the NIBP. Evaluation results showed that, overall, 83% of the bednets surveyed has been impregnated, and 77% of children under the age of five years and 78% of women of childbearing age were reported to be sleeping under impregnated bednets.

PIP: On the basis of pilot studies indicating that bednets impregnated with the insecticide Permethrin are an effective, acceptable method of malaria control, the Gambian government introduced the National Impregnated Bednet Program (NIBP) in 1992. Implementation activities included sensitization sessions with government officials, representatives of nongovernmental organizations, local health care workers, and village leaders; an IEC campaign involving posters, t-shirts, radio programming, and a videotape; staff training; and supply ordering and distribution. A compound-by-compound impregnation strategy was used, and women were instructed not to wash the nets until the end of the rainy season (5 months). At the end of 5 months, a cross-sectional survey involving 6 compounds in 221 villages was conducted. Overall bednet use was 73%, while that for bednet impregnation was 83%. 77% of children under 5 years old and 78% of women of childbearing age (those at greatest risk of malaria) were sleeping under impregnated nets in program villages. During the first year of the intervention, a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages. Although the insecticide was provided free of charge by the government, continued subsidy is not feasible and some form of cost recovery must be developed.

Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme.

After the success of a controlled trial of insecticide-treated bednets in lowering child mortality, The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) in 1992 with the objective of introducing this form of malaria control into all large villages in The Gambia. Five areas (population 115,895) were chosen as sentinel sites for evaluation of the NIBP. During the first year of intervention a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages (rate ratio 0.75 [95% CI 0.57-0.98], p = 0.04). If one area where the programme was ineffective was excluded, the reduction was 38% (0.62 [0.46-0.83), p = 0.001). A decrease in rates of parasitaemia and high-density parasitaemia, an increase in mean packed-cell volume (rate ratio 0.75 [95% CI 0.59-0.98], p = 0.04) and an improvement in the nutritional status of children living in treated villages were also detected. In a country such as The Gambia, where nets were widely used and which has a good primary health care system, it is possible to achieve insecticide-treatment of bednets at a national level with a significant reduction in child mortality; but at a cost which the country cannot afford.

Epidemic poliomyelitis in The Gambia following the control of poliomyelitis as an endemic disease. II. Clinical efficacy of trivalent oral polio vaccine.

An epidemic of poliomyelitis caused by poliovirus type 1 occurred in The Gambia from May to November 1986. Descriptive findings and vaccination coverage levels are reported in part I. This article (part II) describes a case-control study to estimate the clinical efficacy of three or more doses of trivalent oral polio vaccine compared with zero doses. "Cases" were 1- to 7-year-old children paralyzed during the epidemic who were diagnosed as having poliomyelitis by designated referral physicians. They were identified by reports from referral physicians during the epidemic and by a nationwide village-to-village search after the epidemic. Up to five controls were randomly selected for each case from among children of the same age and sex living in neighboring households. In a matched analysis of 195 cases and 839 controls, the efficacy of three or more doses of trivalent oral polio vaccine was 72% (95% confidence interval 57-82) when children without vaccination cards were considered unvaccinated. The efficacy of three or more doses in 1- to 2-year-old children, in whom the determination of vaccination status was considered to be more accurate than in older children, was 81% (95% confidence interval 66-90). Vaccine failure was not associated with short intervals between doses. Higher levels of vaccination coverage and efficacy than those achieved in The Gambia may be needed in African countries to prevent the return of poliomyelitis as an epidemic disease after it has been controlled as an endemic disease.

Knowledge of AIDS, use of condoms and results of counselling subjects with asymptomatic HIV2 infection in The Gambia.

A questionnaire administered to subjects seen during a serological survey in The Gambia revealed that knowledge of AIDS and HIV infection was limited. Males, those with a secondary education and people who lived in urban areas had a better understanding but only 17% of women seen in rural areas had any knowledge of the condition. Only 8% of the subjects seen had used condoms in the preceding 12 months; during this time half of them had done so on less than five occasions. Subjects with a secondary education were more likely to have used condoms. A counsellor met 31 asymptomatic seropositive subjects identified during this survey on two occasions. In the majority, the information given caused anxiety rather than modification of behaviour and, at the time of the second interview, only one subject had discussed the situation with the partner and begun using condoms. Some of the cultural factors which may affect the outcome of counselling in an African society are discussed in the light of these findings.

PIP: Questionnaires given to people from rural and urban populations seen during a serological survey in The Gambia revealed knowledge about AIDS and HIV infection to be limited. Data was received on 1,898 subjects aged at least 15 years. While only 17% of women in rural areas were aware of the existence of AIDS, males, those with secondary education, and those in urban areas demonstrated better understanding of the disease. 8%, however had used condoms over the past 12 months, with 1/2 doing so on less than 5 occasions. Secondary education generally signaled greater likelihood of condom use among respondents. A counsellor met with 31 asymptomatic, HIV-positive subjects in their homes on 2 occasions during the survey. Failing to generate behavior modifications, information provided by the counsellor largely produced anxiety. By the 2nd interview, only 1 subject had discussed AIDS and HIV infection with the partner and began using condoms. Health education programs targeted to underserved rural areas, women, and those without secondary education are severely needed. Radio, used as the key mode of message dissemination, is challenged on the basis of its audience being potentially limited due to gender and/or socioeconomic factors. Limited education, limited knowledge of AIDS in the community as a whole, sociocultural and attitudinal factors fostering social rejection of the seropositive individual, and gaining acceptability for the condom are potential obstacles to effective counselling for improved education and behavioral change. Joint sessions with partners, group sessions, and repeated exposure to a counsellor are suggested approaches. Research is suggested for alternative approaches.

Integrated project plan for the Gambia.

PIP: According to the provisional 1983 census report of the Central Statistics Department, the population of the Gambia was 687,817 in 1983 with 342,134 males and 345,683 females, the 1st time in the country's census history that females outnumbered males. In recognition of the country's high population growth rate and its limited resources and economic prospects, which have brought about a rapid increase in the aggregate basic needs of the population for goods and services, the government has stated its policy and objective on population to reduce mortality, fertility, and immigration rates. For this to happen, the integration of family planning in the existing maternal and child health services was necessary. Alongside with the government's population policy goes a family planning policy that acknowledges that family planning is needed to obtain a better balance between family needs and the means to satisfy those needs, to reduce the number of abortions and the risk of death, to improve the health of mother and children, to intensify child and motherhood care, and to improve child nutrition, education, and the family economy in general. A number of factors still hinder the countrywide availability and accessibility to family planning services. The most salient are: 1) age, 2) number of trained personnel, 3) resources, 4) socio-cultural factors, and 5) accessibility. A national health development project designed to extend primary health care services has recently been launched by the government but to date, not all the aspects of the intervention have been started.^ieng

The need for an integrated approach to the provision of essential health care services: a study from the Gambia.

PIP: Some aspects of the type or preparatory work that can be useful to planning and managers when developments to increase the coverage of health care are being considered are presented. In 1979 the Gambia declared its commitment to a primary health care policy. There are 3 main acute hospitals in the Gambia--2 operated by government and 1 operated by the Medical Research Council. It was decided to review the details of a representative sample of patients admitted to each of the hospitals for 1978. While in 1971, only 14% of all patients admitted to the Royal Victoria Hospital (RVH) in Banjul came from further than 25 miles away, this had increased to 22% in 1978 and for general medicine it has almost doubled from 18-32%. The catchment area of the Bansang Hospital is also quite large. Located less than 10 miles from the "border" with Senegal, a significant proportion of its inpatients come from across the border. In the Medical Research Council Hospital, where clinical research is stressed, the diagnoses of patients are less representative of the more prevalent serious diseases seen in the Gambia. By a combination of the data on the distances travelled to the various hospitals with that on the distribution of the population, it is possible to estimate hospitalization rates for people living in different parts of the country. There appears to be large variations in admission rates for people living in different parts of Gambia. Persons living within 5 miles of Banjul and Bansang, i.e., just over 10% of the total population, have admission rates over 5 times greater than the over 55% living further than 25 miles from these centers. During the visits made to rural health centers, dispensaries, and sub-dispensaries, several areas were identified which are likely to affect the efficient working of those units. These include: difficulties concerning the availability of reliable transport; a lack of adequate basic equipment; buildings and furnishings in need of repair; and inadequate and irregular allocation of essential and basic drug supplies. Patients did not usually travel far to rural facilities for outpatient care. If the provision of primary health care by community health workers is to have a reasonable chance of success, then it is essential that its development be integrated with the existing health service system. It is also critical that the rural basic health services are sufficiently well managed to provide effective support to the primary health care workers.^ieng