A primary goal of MTAT is the reduction of parasit- aemia in the population amongst individuals not experi- encing symptoms severe enough to motivate them to visit a health facility. As a result, the success of these in- terventions depends largely upon the participation of the large majority of the population, even when the per- ceived personal benefit may be low . However, little is known regarding individual and community percep- tions, acceptability, and adherence associated with these community-wide test and treat activities and how these factors may influence programme effectiveness. In-depth understanding of these factors is, therefore, crucial to interpreting the results of completed intervention rounds, and improving the effectiveness of the programme for future rounds and developing strategies for scale-up in new communities. Previous research suggests that while general knowledge of malaria and appropriate treatment for clinical malaria may be high in target communities, un- derstanding the treatment rationale, and, therefore, adher- ence with treatment, may be low for individuals not experiencing symptoms during a test and treat campaign . Additionally, there may be difficulties associated with delivery of these interventions through community health workers (CHWs) if they are not seen by the community as properly trained .
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Brazil has adopted combination prevention, which is a strategy that involves post-exposure prophylaxis (PEP); PrEP; mass campaigns to encourage condom use and testing; distribution of condoms; and specific HIV pre- vention actions with key populations . Indeed, in- creasing access to prevention and diagnosis, particularly for the key populations affected by the epidemic, was key to the success of the Test and Treat strategy. Stand- ing out amongst these efforts is the programme Viva Melhor Sabendo (Live Better Knowing), which was im- plemented in 2013 . The programme consists of out- reach peer prevention intervention that offers rapid oral fluid HIV testing in the community . The Depart- ment of Sexually Transmitted Infections, AIDS, and Viral Hepatitis has worked closely with civil society or- ganizations to implement this programme. This close collaboration has been also essential to link HIV cases detected with the health system . Between January 2013 and April 2016, 43,358 participants were tested, and roughly half (52.1%) were tested for HIV first time ever . These results suggest that the programme is reaching people with low access to testing and who might belong to high-risk groups . However, efforts are still needed to promote testing, particularly amongst the most vulnerable groups.
The use of laboratory diagnosis for malaria treatment in the two facilities was limited to 49%, relying substantially on presumptive diagnosis, contrary to the test and treat recommendations of current guidelines. This indicates high incidence of over-diagnosis and over-use of antimal- arial drugs, in view of the degree of inaccuracy associated with presumptive malaria treatment [15,21,22]. The find- ing corroborates previous studies in Nigeria and other African countries which have reported widespread limited use of laboratory diagnosis in malaria treatment, even with the presence of diagnostic tools [3,8,15,21]. It reflects the level of confidence and popularity to which prescribers at- tach to presumptive malaria treatment, as was confirmed by doctors’ responses. This is consistent with findings by Onwujekwe et al. in 2009 and Uzochukwu et al., in 2010, in which over 80% of providers at both hospital and non- hospital alike, are confident in clinical diagnosis of malaria [10,21]. The study by Meremikwu et al. in 2007, reported laboratory test rate of 45% , while Uzochukwu et al. re- ported a rate of 51.1% in Enugu , suggesting no signifi- cant improvement since 2010. The level of confidence in clinical diagnosis should be considered unrealistic in view of the evidence to the contrary and the high incidence of inaccuracy and wastages associated with presumptive mal- aria treatment . Consequences include missed diagno- sis of other illnesses and increased risk of morbidity . This underscores the need for intensified efforts at promot- ing the use of diagnostic approach to malaria treatment at the facilities, through regular education programmes for health workers . In addition, findings also suggest that low utilisation of diagnostic test was due to high patient load and hence, lack of waiting time for receiving the result of the test, which should be noted for improvement. The benefit of RDT in terms of rapid delivery of results ad- dresses this problem. Patients were treated presumptively even with the availability of laboratory tools in the facilities. The proportion of patients who received antimalarial drugs with slide negative results was quite substantial, consider- ing the enormous wastages that accompany this. This was justified by the prescribers for a number of reasons; (1) un- reliability of laboratory results due to poor laboratory re- agents, (2) RDT insensitivity (further studies may be Table 4 Medication cost of treatment
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The systems effectiveness of MCM or febrile case management has rarely been modelled outside of Africa and never in Papua New Guinea (PNG), a malarious country of approxi- mately 7.3 million people in the Western Pacific. A national survey of health worker compli- ance conducted in the 12-month period following the introduction of a ‘ test and treat ’ protocol in PNG produced results illustrative of the potential tension between MCM only and extended febrile case maangement systems effectiveness models . Health worker compliance with the test and treat MCM protocol was relatively high with 68.3% of febrile patients tested for malaria infection by microscopy or RDT and 98.2% of parasitologically confirmed cases pre- scribed an ACT. Nevertheless, when taking all diagnostic pathways into consideration, only 31.6% of febrile patients prescribed an antimalarial had parasitologically confirmed malaria and only 19.3% of antimalarial prescriptions were ACTs . Thus, a large proportion of febrile cases were still inappropriately treated with antimalarials and the majority of antimalar- ial prescriptions were for obsolete, ineffective medications.
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Assumption 1: “ diagnosis based on clinical features alone has very low specificity and results in over-treatment“ The specificity of a diagnostic algorithm or test almost always varies according to the prevalence of the target condition. Clinical diagnosis and parasitological tests for malaria are no exception. The specificity of clinical diag- nosis of malaria varies according to age group, time, place and the epidemiology of the disease. In low-trans- mission settings, specificity of clinical diagnosis is low and specificity of parasitological tests (e.g. rapid diagnos- tic tests - RDTs) is high, whereas in high-transmission areas the reverse is the case. In children in a high- transmission setting, during the rainy season, high fever of short duration, with no other obvious cause, is most likely to be malaria . In some such settings over 80% of febrile patients (all ages) with presumed malaria are parasite positive, and the “ test and treat ” strategy is not cost-effective, particularly in children and where the cost of treatment is lower than that of the test [8,9].
Similar to HIV status, there was no association between recent drug and alcohol use and being newly diagnosed with HIV in this sample, which may be explained by the high rates of HIV testing in the sample. Although 90% of the entire sample and 95% of women who tested positive for HIV reported a previous HIV test, 36% of women with a positive test were unaware of their status. Among the 92 newly diagnosed women who reported a previous HIV test, the median number of months since their most recent test was 23. To achieve the goal of 90% of HIV-positive women in this population knowing their HIV status, more women need to be tested, and they must be tested more frequently—preferably at least once a year and more fre- quently, if symptomatic. Because almost all of these women likely acquired HIV through sex with men, increases in HIV testing and treatment among women must be accompa- nied by similar increases among men to reduce incidence. Unfortunately, efforts to test and treat Black African men in South Africa have been less successful [26, 27].
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settings clinicians should be encouraged to take clinical de- cisions and use scarce resources rationally. Moreover, clin- ical decision-making is nor linear or static, rather an iterative process. Every follow-up consultation the clinician will re-assess the patient. New signs may emerge, and thus alter the clinical decision-making process. The described structured and objective approach may not be feasible to conduct during every clinical consultation, however, the concepts of confirming and excluding power and test-treat threshold may provide structure to the clinician when rul- ing in or out a diagnosis.
UNAIDS recently published ambitious new targets to ‘end the AIDS epidemic by 2030’ . To achieve this, it will be necessary to intensively scale-up HIV care pro- grammes and ART provision throughout sub-Saharan Africa. A ‘universal test and treat’ policy – combining large-scale programmes of HIV testing with universal ac- cess to ART – is frequently promoted as a way of greatly reducing HIV incidence and mortality. We demonstrate that improving retention on ART should also constitute a key policy component in the drive to eliminate HIV. For this reason, we advocate a ‘universal test, treat, and keep’ policy.
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The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART). To confront with the complexity of assessment on this policy, the elimination threshold or the effective reproduction number has been proposed for its use in determining the overall success to anticipate the eventual elimination. Since the publication of original model in 2009, key issues of test-and-treat modeling studies have been identified, including theoretical problems surrounding the sexual partnership network, heterogeneities in the transmission dynamics, and realistic issues of achieving and maintaining high treatment coverage in the most hard-to-reach populations. To explicitly design country-specific control policy, quantitative modeling approaches to each single setting with differing epidemiological context would require multi-disciplinary collaborations among clinicians, public health practitioners, laboratory technologists, epidemiologists and mathematical modelers.
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After 30 years of treatment with Mectizan (ivermectin), cutaneous and ocular complications of Onchocerca volvulus infection are now scarce in endemic communities. Indeed, transmission has been interrupted and the O. volvulus- associated disease has disappeared in some African foci. Despite this success, onchocerciasis elimination in Loa loa co-endemic areas is still constrained by severe adverse events (SAEs) occurring after ivermectin treatment in some individuals harbouring very high L. loa micro ﬁ laremia. One approach towards the prevention of these SAEs is to identify individuals with high L. loa microﬁlaremia and exclude them from ivermectin treatment. The development of the LoaScope has provided the tool that underlies this test and not treat (TaNT) strategy. The ﬁrst successful TaNT campaign was conducted in a L. loa highly endemic focus in Cameroon in 2015 without any SAEs. To accomplish this within a research setting, 60 people were deployed for this campaign, making this ‘research’ strategy not sustainable from a cost perspective. We describe here a way of reducing the cost of the TaNT strategy with a smaller team (three people) selected within affected communities. We also suggest the organization of a TaNT campaign in affected countries.
Routine care comprised of outpatient registration, tri- age of patients by nurses, and care given by attending doctors to patient which consists of history, general examination, followed by either laboratory request or direct treatment based on history and examination by doctors at SGH. The test treat package (intervention) was tested against routine out patient management of fever by doctors at SGH (control). Patients randomized to the test-treat group underwent a structured clinical examination consisting of ear, nose, throat and joint in- spection and chest auscultation after their history had been taken. A bed side malaria RDT for all Plasmodium species (Parascreen; Zephyr Biomedicals, India) was per- formed according to the manufacturer’s specifications. Thick and thin blood films for malaria was done for all participants in the intervention group. All the RDTs were done and interpreted by one of the authors (EA) to eliminate inter-observer bias. A urine sample was ob- tained from each child in the intervention group, either spontaneously or by catheterization for children under two years old who could not produce urine on demand. These were then immediately tested at the bedside for nitrites and leucocytes using combi-10 urine dipsticks. Samples that tested positive for nitrite and/or leucocytes were transported immediately to the microbiology la- boratory of the local Teaching Hospital (KATH) for cul- ture and sensitivity.
There are many other factors that should be considered before the introduction of screening programs . More information is required about the balance of harms and benefits of screening, the acceptability and feasibility of H. pylori infection screening tests, the capacity of the health care system particularly primary care, and potential ethical issues about identifying infection and being unable to treat it in some cases. Policy-makers would also need to con- sider the relative cost-effectiveness and potential equity gains of alternative interventions in high-income countries such as tobacco control, obesity control and other screen- ing programs (for example colorectal cancer, chronic kidney disease and lung cancer in ex-smokers).
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Planning to avoid weaknesses and threats by focusing on the program strengths will minimize problems on the trip and during the health post clinical time. Health post workers and volunteers are benevolent and altruistic, yet in their efforts they may try to give medical care outside the scope of their medical license and knowledge base. An informal inquiry found that health post worker did not understand the difference between the signs and symptoms of H. pylori, dyspepsia and other gastrointestinal entities. Filling this knowledge gap was incorporated into the H. pylori test and treat program that focuses on the right treatment being prescribed for the right condition (see Appendix R).
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These results suggest that without additional preven- tion measures, the optimal global incidence reduction strategy for hepatitis C is to implement targeted test and treat programmes among those at high risk of hepatitis C infection and to implement hepatitis C vaccination through these programmes. It is estimated that only 20% of people with hepatitis C were diagnosed globally in 2015 , meaning that broad screening programmes will be required among risk populations in most settings to achieve elimination. This would provide an opportun- ity to achieve relatively high vaccination coverage, in particular among PWID. In addition, for settings with high rates of transmission in the general community, the model suggests that introduction of a vaccination programme for adolescents would provide additional benefit (Additional file 1: Appendix C—Table S4, generalised settings). It is therefore worth examining the potential to combine a hepatitis C vaccine with other vaccines targeting this age group such as human papillo- mavirus or hepatitis B.
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Abstract: In clinical development of a test treatment under investigation, clinical trials are often conducted for evaluation of safety and efficacy of the test treatment. To provide an accurate and reliable assessment, adequate and well-controlled clinical trials using valid study designs are necessarily conducted for obtaining substantial evidence of safety and efficacy of the test treat- ment under investigation. In practice, however, some debatable issues are commonly encountered regardless compliance with good statistics practice and good clinical practice. These issues include, but are not limited to: 1) appropriateness of statistical hypotheses for clinical investiga- tion; 2) correctness of power analysis assumptions; 3) integrity of randomization and blinding; 4) post hoc endpoint selection; 5) impact of protocol amendments on the characteristics of the trial population; 6) multiplicity in clinical trials; 7) missing data imputation; 8) adaptive design methods; and 9) independence of a data monitoring committee. In this article, these issues are briefly described. The impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation are discussed with examples whenever applicable. Some recommendations regarding possible resolutions of these issues are also provided.
evident within months. In the same cohort of patients, function improved as judged by increases in 6-min walk test (6MWT) and BOT-2 test of motor proficiency . These improvements were observed to persist through- out the duration of the study. Additional evaluation of a similarly aged cohort of treated and control patients for mobility noted similar impairments at baseline followed by significantly greater rate of improvement in assess- ment scores for treated versus control patients . Hypotonia is also a common concern in patients with childhood hypophosphatasia. Additional investigation has shown that patients had substantial muscle weakness and other physical limitations as compared to their peers, but after several years of treatment they experi- enced persistent improvement in muscle strength, agility, and pain [23, 24]. Craniosynostosis and abnormal dentition are also well-described features of hypophop- sphatasia, but it is not known that therapy with asfotase alfa alters their natural history.
All included studies had limitations to a greater or lesser extent. None of the included models is able to completely capture the complexity of managing patients with dyspep- tic complaints. This is due to the use of one-dimensional outcome measures, insufficient consideration of thera- peutic implications and follow-ups, time horizons which are too short or unverifiable determination of utility values and social costs. Furthermore, it must be considered that a cost-effectiveness comparison between alternative management strategies is limited in several economic analyses. In the majority of the included studies, disease specific outcome measures are used. Due to the lack of expert literature on threshold values for incremental outcome gains, the reported incremental cost-effectiven- ess ratios cannot be assessed. Therefore, conclusions on the cost-effectiveness of test-and-treat using the urea breath test in comparison to other strategies can only be drawn for dominant cost-effectiveness ratios.
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The goal of a screen-and-treat programme for cervical cancer is to reduce cervical cancer and related mortality with relatively few adverse events. The programme must include a screening test or strategy (sequence of tests) and be linked to appropriate treatments for CIN, and also provide referral for treatment of women with invasive cervical cancer. Common screening tests that are widely used include tests for human papillomavirus (HPV), cytology (Pap test), and unaided visual inspection with acetic acid (VIA). These tests can be used as a single test or in a sequence. When using a single test, a positive result indicates the need for treatment. When using a sequence of tests, women who test positive on the first test receive another test and only those who test positive on the second test are treated. Women with a positive first screening test followed by a negative second screening test are followed up.
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not febrile. On counterchecking the parasitological results of the patients who received anti-malarials prior to labora- tory results, 84.0% were RDT-negative who should not otherwise have received anti-malarial medication. One as- sumption that could be made is that this category of health workers (who prescribed for the 19.4% patients) may perhaps not trust the laboratory results yet, or that they remain with the orientation of prescribing an anti- malarial under the Integrated Management of Childhood Illness (IMCI) guidelines (although the absence of fever in most cases contradicts this). Chibombo district was most affected by prescriber preference to treat with an anti-malarial before the laboratory results (53.6%). It’s encouraging however, to generally note that the number of children in this study who were treated before labora- tory results were fewer.
Conditions precedent for allowance of depreciation is that the assets shall be owned, wholly or partly by the assessee and used for the purposes of his business or profession. Depreciation is treated as allowance under section 32(2). Depreciation allowance is a reduction which is granted by the State in order for the calculation of income which is centered on numerous factors which are relevant to full fiscal administration. It signifies reduction in the worth of the asset when applied to making revenues. Under this section depreciation allowance is statutory and is not limited clearly to depreciation in the value of asset by purpose of wear and tear. It may be permissible according to accounting principles. Once asset merged into block it does not have separate identity evidence of use. Though amalgamation, reduction and disallowance of depreciation could not be dealt in the paper due to constraint of words. So we concentrated specifically on User Test and allowance of depreciation. It is therefore always desirable to establish the actual use and authorisation for the same from employers and government authorities whenever