Efficacy of antipsychotics in delusional infestation.

BACKGROUND: Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI). OBJECTIVES: We evaluated the treatment responses associated with different antipsychotics in DI patients. METHODS: We undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow-up Clinical Global Impression Scale (CGI-S) score. The CGI-S is a validated psychiatric research tool. Participants were excluded if they had known limited or non-adherence to an antipsychotic, or if no CGI-S scores were present at follow-up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI-S score. The last available CGI-S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow-up CGI-S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow-up CGI-S scores. Differences in CGI-S changes between antipsychotic episodes were tested by analysis of variance (ANOVA). RESULTS: In total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28). CONCLUSIONS: Amisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first-line treatment options in DI patients.

Screening for post-TB lung disease at TB treatment completion: Are symptoms sufficient?

Pulmonary TB survivors face a high burden of post-TB lung disease (PTLD) after TB treatment completion. In this secondary data analysis we investigate the performance of parameters measured at TB treatment completion in predicting morbidity over the subsequent year, to inform programmatic approaches to PTLD screening in low-resource settings. Cohort data from urban Blantyre, Malawi were used to construct regression models for five morbidity outcomes (chronic respiratory symptoms or functional limitation, ongoing health seeking, spirometry decline, self-reported financial impact of TB disease, and death) in the year after PTB treatment, using three modelling approaches: logistic regression; penalised regression with pre-selected predictors; elastic net penalised regression using the full parent dataset. Predictors included demographic, clinical, symptom, spirometry and chest x-ray variables. The predictive performance of models were examined using the area under the receiver-operator curve (ROC AUC) values. Key predictors were identified, and their positive and negative predictive values (NPV) determined. The presence of respiratory symptoms at TB treatment completion was the strongest predictor of morbidity outcomes. TB survivors reporting breathlessness had higher odds of spirometry decline (aOR 20.5, 95%CI:3-199.1), health seeking (aOR 10.2, 2.4-50), and symptoms or functional limitation at 1-year (aOR 16.7, 3.3-133.4). Those reporting activity limitation were more likely to report symptoms or functional limitation at 1-year (aOR 4.2, 1.8-10.3), or severe financial impact of TB disease (aOR2.3, 1.0-5.0). Models were not significantly improved by including spirometry or imaging parameters. ROC AUCs were between 0.65-0.77 for the morbidity outcomes. Activity limitation at treatment completion had a NPV value of 78-98% for adverse outcomes. Our data suggest that whilst challenging to predict the development of post-TB morbidity, the use of symptom screening tools at TB treatment completion to prioritise post-TB care should be explored. We identified little benefit from the additional use of spirometry or CXR imaging.

Comparing Additionality of Tuberculosis Cases Using GeneXpert or Smear-Based Active TB Case-Finding Strategies among Social Contacts of Index Cases in Nepal.

This study compares the yield and additionality of community-based active tuberculosis (TB) active case-finding strategies using either smear microscopy or GeneXpert as the TB diagnostic test. Active case-finding strategies screened social contacts of index cases and high-risk groups in four districts of Nepal in July 2017-2019. Two districts (Chitwan and Dhanusha) applied GeneXpert testing and two districts (Makwanpur and Mahotarri) used smear microscopy. Two control districts implemented standard national TB program activities. Districts implementing GeneXpert testing screened 23,657 people for TB, tested 17,114 and diagnosed 764 TB cases, producing a yield of 4.5%. Districts implementing smear microscopy screened 19,961 people for TB, tested 13,285 and diagnosed 437 cases, producing a yield of 3.3%. The screening numbers required were 31 for GeneXpert and 45.7 for smear districts. The test numbers required were 22.4 and 30.4 for GeneXpert and smear. Using the TB REACH additionality method, social contact tracing for TB through GeneXpert testing contributed to a 20% (3958/3322) increase in district-level TB notifications, smear microscopy 12.4% (3146/2798), and -0.5% (2553/2566) for control districts. Therefore, social contact tracing of TB index cases using GeneXpert testing should be implemented throughout Nepal within the TB FREE initiative to close the notification gap and accelerate progress toward END TB strategy targets.

Clinical Impact of the Line Probe Assay and Xpert® MTB/RIF Assay in the Presumptive Diagnosis of Drug-Resistant Tuberculosis in Brazil: A Pragmatic Clinical Trial.

BACKGROUND: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert. METHODS: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months. RESULTS: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p<0.01) in arm 1. Compared to the MGIT group, culture conversion after 6 months was higher for Xpert in arm 1 (90.9% vs. 79.3%, p=0.39) and LPA in arm 2 (80.0% vs. 83.0%, p=0.81). CONCLUSIONS: In the Xpert arm, there was a significant reduction in days to the start of appropriate anti-TB treatment and a trend towards greater culture conversion in the sixth month.

Accuracy of computer-aided chest X-ray in community-based tuberculosis screening: Lessons from the 2016 Kenya National Tuberculosis Prevalence Survey.

Community-based screening for tuberculosis (TB) could improve detection but is resource intensive. We set out to evaluate the accuracy of computer-aided TB screening using digital chest X-ray (CXR) to determine if this approach met target product profiles (TPP) for community-based screening. CXR images from participants in the 2016 Kenya National TB Prevalence Survey were evaluated using CAD4TBv6 (Delft Imaging), giving a probabilistic score for pulmonary TB ranging from 0 (low probability) to 99 (high probability). We constructed a Bayesian latent class model to estimate the accuracy of CAD4TBv6 screening compared to bacteriologically-confirmed TB across CAD4TBv6 threshold cut-offs, incorporating data on Clinical Officer CXR interpretation, participant demographics (age, sex, TB symptoms, previous TB history), and sputum results. We compared model-estimated sensitivity and specificity of CAD4TBv6 to optimum and minimum TPPs. Of 63,050 prevalence survey participants, 61,848 (98%) had analysable CXR images, and 8,966 (14.5%) underwent sputum bacteriological testing; 298 had bacteriologically-confirmed pulmonary TB. Median CAD4TBv6 scores for participants with bacteriologically-confirmed TB were significantly higher (72, IQR: 58-82.75) compared to participants with bacteriologically-negative sputum results (49, IQR: 44-57, p<0.0001). CAD4TBv6 met the optimum TPP; with the threshold set to achieve a mean sensitivity of 95% (optimum TPP), specificity was 83.3%, (95% credible interval [CrI]: 83.0%-83.7%, CAD4TBv6 threshold: 55). There was considerable variation in accuracy by participant characteristics, with older individuals and those with previous TB having lowest specificity. CAD4TBv6 met the optimal TPP for TB community screening. To optimise screening accuracy and efficiency of confirmatory sputum testing, we recommend that an adaptive approach to threshold setting is adopted based on participant characteristics.

Stakeholder perspectives around post-TB wellbeing and care in Kenya and Malawi.

BACKGROUND: There is growing awareness of the burden of post-TB morbidity, and its impact on the lives and livelihoods of TB affected households. However little work has been done to determine how post-TB care might be delivered in a feasible and sustainable way, within existing National TB Programmes (NTPs) and health systems, in low-resource, high TB-burden settings. In this programme of stakeholder engagement around post-TB care, we identified actors with influence and interest in TB care in Kenya and Malawi, including TB-survivors, healthcare providers, policy-makers, researchers and funders, and explored their perspectives on post-TB morbidity and care. METHODS: Stakeholder mapping was completed to identify actors with interest and influence in TB care services in each country, informed by the study team's local, regional and international networks. Key international TB organisations were included to provide a global perspective. In person or online one-to-one interviews were completed with purposively selected stakeholders. Snowballing was used to expand the network. Data were recorded, transcribed and translated, and a coding frame was derived. Data were coded using NVivo 12 software and were analysed using thematic content analysis. Online workshops were held with stakeholders from Kenya and Malawi to explore areas of uncertainty and validate findings. RESULTS: The importance of holistic care for TB patients, which addresses both TB comorbidities and sequelae, was widely recognised by stakeholders. Key challenges to implementation include uncertainty around the burden of post-TB morbidity, leadership of post-TB services, funding constraints, staff and equipment limitations, and the need for improved integration between national TB and non-communicable disease (NCD) programmes for care provision and oversight. There is a need for local data on the burden and distribution of morbidity, evidence-informed clinical guidelines, and pilot data on models of care. Opportunities to learn from existing HIV-NCD services were emphasised. DISCUSSION: This work addresses important questions about the practical implementation of post-TB services in two African countries, exploring if, how, where, and for whom these services should be provided, according to a broad range of stakeholders. We have identified strong interest in the provision of holistic care for TB patients in Kenya and Malawi, and key evidence gaps which must be addressed to inform decision making by policy makers, TB programmes, and funders around investment in post-TB services. There is a need for pilot studies of models of integrated TB care, and for cross-learning between countries and from HIV-NCD services.

Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study.

RATIONALE: Pulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited. OBJECTIVES: To describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period. METHODS: Adults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling. MEASUREMENT AND MAIN RESULTS: We recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion. CONCLUSION: Spirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV1 decline). Effective interventions are needed to improve the care of this group of patients.

Clinical Impact of the Line Probe Assay and Xpert® MTB/RIF Assay in the Presumptive Diagnosis of Drug-Resistant Tuberculosis in Brazil: A Pragmatic Clinical Trial

ABSTRACT Background: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert. Methods: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months. Results: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p<0.01) in arm 1. Compared to the MGIT group, culture conversion after 6 months was higher for Xpert in arm 1 (90.9% vs. 79.3%, p=0.39) and LPA in arm 2 (80.0% vs. 83.0%, p=0.81). Conclusions: In the Xpert arm, there was a significant reduction in days to the start of appropriate anti-TB treatment and a trend towards greater culture conversion in the sixth month.

'If not TB, what could it be?' Chest X-ray findings from the 2016 Kenya Tuberculosis Prevalence Survey.

BACKGROUND: The prevalence of diseases other than TB detected during chest X-ray (CXR) screening is unknown in sub-Saharan Africa. This represents a missed opportunity for identification and treatment of potentially significant disease. Our aim was to describe and quantify non-TB abnormalities identified by TB-focused CXR screening during the 2016 Kenya National TB Prevalence Survey. METHODS: We reviewed a random sample of 1140 adult (≥15 years) CXRs classified as 'abnormal, suggestive of TB' or 'abnormal other' during field interpretation from the TB prevalence survey. Each image was read (blinded to field classification and study radiologist read) by two expert radiologists, with images classified into one of four major anatomical categories and primary radiological findings. A third reader resolved discrepancies. Prevalence and 95% CIs of abnormalities diagnosis were estimated. FINDINGS: Cardiomegaly was the most common non-TB abnormality at 259 out of 1123 (23.1%, 95% CI 20.6% to 25.6%), while cardiomegaly with features of cardiac failure occurred in 17 out of 1123 (1.5%, 95% CI 0.9% to 2.4%). We also identified chronic pulmonary pathology including suspected COPD in 3.2% (95% CI 2.3% to 4.4%) and non-specific patterns in 4.6% (95% CI 3.5% to 6.0%). Prevalence of active-TB and severe post-TB lung changes was 3.6% (95% CI 2.6% to 4.8%) and 1.4% (95% CI 0.8% to 2.3%), respectively. INTERPRETATION: Based on radiological findings, we identified a wide variety of non-TB abnormalities during population-based TB screening. TB prevalence surveys and active case finding activities using mass CXR offer an opportunity to integrate disease screening efforts. FUNDING: National Institute for Health Research (IMPALA-grant reference 16/136/35).

The long term effect of pulmonary tuberculosis on income and employment in a low income, urban setting.

BACKGROUND: Mitigating the socioeconomic impact of tuberculosis (TB) is key to the WHO End TB Strategy. However, little known about socioeconomic well-being beyond TB-treatment completion. In this mixed-methods study, we describe socioeconomic outcomes after TB-disease in urban Blantyre, Malawi, and explore pathways and barriers to financial recovery. METHODS: Adults ≥15 years successfully completing treatment for a first episode of pulmonary TB under the National TB Control Programme were prospectively followed up for 12 months. Socioeconomic, income, occupation, health seeking and cost data were collected. Determinants and impacts of ongoing financial hardship were explored through illness narrative interviews with purposively selected participants. RESULTS: 405 participants were recruited from February 2016 to April 2017. Median age was 35 years (IQR: 28-41), 67.9% (275/405) were male, and 60.6% (244/405) were HIV-positive. Employment and incomes were lowest at TB-treatment completion, with limited recovery in the following year: fewer people were in paid work (63.0% (232/368) vs 72.4% (293/405), p=0.006), median incomes were lower (US$44.13 (IQR: US$0-US$106.15) vs US$72.20 (IQR: US$26.71-US$173.29), p<0.001), and more patients were living in poverty (earning

Reducing delays to multidrug-resistant tuberculosis case detection through a revised routine surveillance system.

BACKGROUND: Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. METHODS: Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. RESULTS: The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). CONCLUSION: Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as 'WhatsApp' and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different contexts.

Patient outcomes associated with post-tuberculosis lung damage in Malawi: a prospective cohort study.

BACKGROUND: Post-tuberculosis lung damage (PTLD) is a recognised consequence of pulmonary TB (pTB). However, little is known about its prevalence, patterns and associated outcomes, especially in sub-Saharan Africa and HIV-positive adults. METHODS: Adult (≥15 years) survivors of a first episode of pTB in Blantyre, Malawi, completed the St George's Respiratory Questionnaire, 6-minute walk test, spirometry and high-resolution CT (HRCT) chest imaging at TB treatment completion. Symptom, spirometry, health seeking, TB-retreatment and mortality data were collected prospectively to 1 year. Risk factors for persistent symptoms, pulmonary function decline and respiratory-related health-seeking were identified through multivariable regression modelling. RESULTS: Between February 2016 and April 2017, 405 participants were recruited. Median age was 35 years (IQR: 28 to 41), 77.3% (313/405) had had microbiologically proven pTB, and 60.3% (244/403) were HIV-positive. At pTB treatment completion, 60.7% (246/405) reported respiratory symptoms, 34.2% (125/365) had abnormal spirometry, 44.2% (170/385) had bronchiectasis ≥1 lobe and 9.4% (36/385) had ≥1 destroyed lobe on HRCT imaging. At 1 year, 30.7% (113/368) reported respiratory symptoms, 19.3% (59/305) and 14.1% (43/305) of patients had experienced declines in FEV1 or FVC of ≥100 mL, 16.3% (62/380) had reported ≥1 acute respiratory event and 12.2% (45/368) had symptoms affecting their ability to work. CONCLUSIONS: PTLD is a common and under-recognised consequence of pTB that is disabling for patients and associated with adverse outcomes beyond pTB treatment completion. Increased efforts to prevent PTLD and guidelines for management of established disease are urgently needed. Low-cost clinical interventions to improve patient outcomes must be evaluated.

A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis.

BACKGROUND: Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS: We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS: Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], -7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, -10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS: In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.).

Routine surveillance for the identification of drug resistant Tuberculosis in Tanzania: A cross-sectional study of stakeholders' perceptions.

BACKGROUND: Routine surveillance is required to monitor the performance of tuberculosis diagnostic programme and is essential for the rapid detection of drug resistance. The main objective of this study was to explore the effectiveness and stakeholder perception of the current routine surveillance system for previously treated tuberculosis cases in Tanzania with a view to identify interventions to improve and accelerate positive patient outcomes. METHODS: A study using quantitative and qualitative methods of data collection including in-depth interviews and focus group discussions with health care service providers was conducted in four regions. Quantitative data were extracted from the routine databases to assess performance. RESULTS: Quantitative findings from 2011 to 2013 showed 2,750 specimens from previously treated TB cases were received at the reference laboratory. The number increased year on year, but even in the most recent year was only 61% of that expected. The median and interquartile range of turnaround time in days from specimen reception to results reported for smear microscopy, culture and drug susceptibility testing were 1(1, 1), 61(43, 71) and 129(72, 170) respectively. Contaminated specimens were reported in 3.6% of cases. The qualitative analysis showed the system of sending specimens using postal services was seen to be efficient by participants. However, there were many challenges and significant delays in specimens reaching the reference laboratory associated with lack of funds to transfer specimens, weak form completion, inadequate training and poor supervision. These all adversely affected the implementation of the routine surveillance system. CONCLUSIONS: Many issues limit the effectiveness of the routine surveillance system in Tanzania. Priority areas for strengthening are; specimen transportation, supervision and availability of commodities. A pilot study of a revised routine surveillance system that takes into account the observations from this study alongside improved access to drug susceptibility testing using Xpert MTB/RIF should be considered.

Enhanced patient research participation: a Photovoice study in Blantyre Malawi.

OBJECTIVES: Patient involvement in palliative care research is a desirable if challenging goal. Photovoice is an action research method in which affected communities gather photographs to document and discuss their communities' strengths and concerns. Engagement with policymakers is a separately stated goal. Photovoice is increasingly used in health-related research but has not been widely described in the palliative care literature. We report on experiences and lessons learnt using Photovoice in Blantyre, Malawi to encourage its wider use in research and practice. METHODS: Thirteen co-researchers (six patients and seven household carers, mean age 47 years) receiving community-based palliative care, attended nine half-day group sessions over a 4-month period. Co-researchers produced, selected and analysed photographs. On completion of data collection, they conducted an advocacy event, including a photographic exhibition, to which media representatives and community leaders were invited. RESULTS: Procedures to ensure safety of co-researchers and to obtain consent of individuals identified in the photographs were developed during the planning phase. Co-researchers engaged with the Photovoice process with enthusiasm, although frailty and physical disability (poor sight) limited participation for some older adults. Inclusion of palliative care staff within the research team helped to facilitate open dialogue and clinical review where appropriate. CONCLUSIONS: In this Photovoice study, patients and family members receiving palliative care engaged in an exploration of household well-being using photography, participatory analysis and an advocacy event. With appropriate planning, Photovoice can be adapted to a range of settings to enhance patient participation.

Longer Duration of Untreated Psychosis is Associated with Poorer Outcomes for Patients with Delusional Infestation.

We examined the association between the duration of untreated psychosis and outcome for patients with delusional infestation. This multi-centre international study included 211 consecutive patients. Illness severity was evaluated at first presentation and outcome was measured with the Clinical Global Impression scale (CGI) at baseline and follow-up. A regression analysis showed a clear clinical and statistically significant association between shorter duration of untreated psychosis and better outcome at follow-up. Patients with a duration of untreated psychosis of less than one year showed a CGI-S change from 5.37 to 2.07; those with a duration of untreated psychosis of 1-5 years a change from 5.48 to 2.59, and those with a duration of untreated psychosis of >5 years a change from 5.59 to 3.37. This difference of 1.1 CGI points between the groups resembles a clinically relevant difference in patient outcome. Our results suggest that longer duration of untreated psychosis in patients with delusional infestation is associated with significantly less favour-able clinical outcomes.

The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.

BACKGROUND: In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. STUDY AIM: The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. METHODS: A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. RESULTS: Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms. CONCLUSION: The results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.

Informal Health Provider and Practical Approach to Lung Health interventions to improve the detection of chronic airways disease and tuberculosis at primary care level in Malawi: study protocol for a randomised controlled trial.

BACKGROUND: In developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at primary health care level are weak and patients turn to unskilled informal health providers to seek health care. Delayed diagnosis and treatment of these diseases facilitates increased severity and tuberculosis transmission. The World Health Organisation developed the Practical Approach to Lung Health strategy which has been shown to improve the management of both tuberculosis and chronic airways disease. The guidelines address the need for integrated guidelines for tuberculosis and chronic airways disease. Engaging with informal health providers has been shown to be effective in improving health services uptake. However, it is not known whether engaging community informal health providers would have a positive impact in the implementation of the Practical Approach to Lung Health strategy. We will use a cluster randomised controlled trial to determine the effect of using the two interventions to improve case detection and treatment of patients with tuberculosis and chronic airways disease. METHODS: A three-arm cluster randomised trial design will be used. A primary health centre catchment population will form a cluster, which will be randomly allocated to one of the arms. The first arm personnel will receive the Practical Approach to Lung Health strategy intervention. In addition to this strategy, the second arm personnel will receive training of informal health providers. The third arm is the control. The effect of interventions will be evaluated by community surveys. Data regarding the diagnosis and management of chronic cough will be gathered from primary health centres. DISCUSSION: This trial seeks to determine the effect of Informal Health Provider and Practical Approach to Lung Health interventions on the detection and management of chronic airways disease and tuberculosis at primary care level in Malawi. TRIAL REGISTRATION: The unique identification number for the registry is PACTR201411000910192--21 November 2014.