Healthcare consumers' perceptions of incentive-linked prescribing: A scoping review.

Incentive-linked prescribing (ILP) is considered a controversial practice universally. If incentivised, physicians may prioritise meeting pharmaceutical sales targets through prescriptions, rather than considering patients' health and wellbeing. Despite the potential harms of ILP to patients and important stakeholders in the healthcare system, healthcare consumers (HCCs) which include patients and the general public often have far less awareness about the practice of pharmaceutical incentivisation of physicians. We conducted a scoping review to explore what existing research says about HCCs' perceptions of the financial relationship between physicians and pharmaceutical companies. To conduct this scoping review, we followed Arksey and O'Malley's five-stage framework: identifying research questions, identifying relevant studies, selecting eligible studies, data charting, and collating, summarising, and reporting results. We also used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses' extension for scoping reviews (PRISMA-ScR), as a guide to organise the information in this review. Quantitative and qualitative studies with patients and the general public, published in the English language were identified through searches of Scopus, Medline (OVID), EMBASE (OVID), and Google Scholar. Three themes emerged through the analysis of the 13 eligible studies: understanding of incentivisation, perceptions of hazards linked to ILP, and HCCs' suggestions to address it. We found documentation that HCCs exhibited a range of knowledge from good to insufficient about the pharmaceutical incentivisation of physicians. HCCs perceived several hazards linked to ILP such as a lack of trust in physicians and the healthcare system, the prescribing of unnecessary medications, and the negative effect on physicians' reputations in society. In addition to strong regulatory controls, it is critical that physicians self-regulate their behaviour, and publicly disclose if they have any financial ties with pharmaceutical companies. Doing so can contribute to trust between patients and physicians, an important part of patient-focused care and a contributor to user confidence in the wider health system.

Efflux pump gene single-nucleotide variants associated with resistance in Mycobacterium tuberculosis isolates with discrepant drug genotypes.

INTRODUCTION: Single-nucleotide variants (SNVs) in Mycobacterium tuberculosis (M. tuberculosis) genomes can predict multidrug resistance (MDR) but not all phenotype-genotype correlations can be explained. We investigated SNVs in efflux pumps (EPs) in the context of M. tuberculosis drug resistance. METHODS: We analysed 2221 M. tuberculosis genomes from 1432 susceptible and 200 MDR, 172 pre-extensively drug resistant (XDR) and 417 XDR isolates. Analysis of 47 EP genes was conducted using MTB-VCF, an in-house bioinformatics pipeline. SNVs were categorized according to their SIFT/Polyphen scores. Resistance genotypes were also called using the TB-Profiler tool. RESULTS: Genome comparisons between susceptible and drug resistant (DR) isolates identified 418 unique SNVs in EP of which; 53.5% were in MDR, 68.9% in pre-XDR and 61.3% in XDR isolates. Twenty EPs had unique SNVs with a high SIFT/PolyPhen score, comprising 38 unique SNVs. Sixteen SNVs across 12 EP genes were significantly associated with drug resistance and enriched in pre-XDR and XDR strains. These comprised 12 previously reported SNVs (in Rv0191, Rv0507, Rv0676, Rv1217, Rv1218, Rv1273, Rv1458, Rv1819, and Rv2688) and 4 novel SNVs (in Rv1877 and Rv2333). We investigated their presence in genomes of 52 MDR isolates with phenotype-genotype discrepancies to rifampicin (RIF), isoniazid (INH), or fluoroquinolones. SNVs associated with RIF and INH (Rv1217_1218, Rv1819, Rv0450, Rv1458, Rv3827, Rv0507, Rv0676, Rv1273, and Rv2333), and with fluoroquinolone (Rv2688) resistance were present in these discrepant strains. CONCLUSIONS: Considering SNVs in EPs as part of M. tuberculosis genome-based resistance interpretation may add value, especially in evaluation of XDR resistance in strains with phenotype-genotype discrepancies.

"Caught In Each Other's Traps": Factors Perpetuating Incentive-Linked Prescribing Deals Between Physicians and the Pharmaceutical Industry.

BACKGROUND: Despite known adverse impacts on patients and health systems, 'incentive-linked prescribing', which describes the prescribing of medicines that result in personal benefits for the prescriber, remains a widespread and hidden impediment to quality of healthcare. We investigated factors perpetuating incentive-linked prescribing among primary care physicians in for-profit practices (referred to as private doctors), using Pakistan as a case study. METHODS: Our mixed-methods study synthesised insights from a survey of 419 systematically samples private doctors and 68 semi-structured interviews with private doctors (n=28), pharmaceutical sales representatives (n=12), and provincial and national policy actors (n=28). For the survey, we built a verified database of all registered private doctors within Karachi, Pakistan's most populous city, administered an electronic questionnaire in-person and descriptively analysed the data. Semi-structured interviews incorporated a vignette-based exercise and data was analysed using an interpretive approach. RESULTS: Our survey showed that 90% of private doctors met pharmaceutical sales representatives weekly. Three interlinked factors perpetuating incentive-linked prescribing we identified were: gaps in understanding of conflicts of interest and loss of values among doctors; financial pressures on doctors operating in a (largely) privately financed health-system, exacerbated by competition with unqualified healthcare providers; and aggressive incentivisation by pharmaceutical companies, linked to low political will to regulate and an over-saturated pharmaceutical market. CONCLUSION: Regular interactions between pharmaceutical companies and private doctors are normalised in our study setting, and progress on regulating these is hindered by the substantial role of incentive-linked prescribing in the financial success of physicians and the pharmaceutical industry employees. A first step towards addressing the entrenchment of incentive-linked prescribing may be to reduce opposition to restrictions on incentivisation of physicians from stakeholders within the pharmaceutical industry, physicians themselves, and policymakers concerned about curtailing growth of the pharmaceutical industry.

What happens when private general practitioners receive incentivisation offers from pharmaceutical sales representatives? A qualitative study in Pakistan.

OBJECTIVES: Pharmaceutical incentivisation of physicians for profit maximisation is a well-documented health system challenge. This study examined general practitioners' (GPs) reactions to pharmaceutical incentivisation offers in one region in Pakistan. METHODS: We used the Standardised Pharmaceutical Sales Representative (SPSR) method and qualitative interviews with GPs. SPSRs were field researchers representing mock pharmaceutical companies who recorded their observations of 267 GPs' responses to pharmaceutical incentivisation offers. We triangulated SPSR data using qualitative interviews with a subset of the same GPs to gather information about how they interpreted different interaction outcomes. RESULTS: We found four major outcomes for GPs being offered incentives by pharmaceutical companies for prescribing medications. GPs might agree to make incentivisation deals, reject incentivisation offers, disallow PSRs to access them, or remain indeterminate with no clear indication of acceptance or rejection of incentivisation offers. GPs rejecting SPSRs' incentivisation offers indicated having active commitments to other pharmaceutical companies, not being able to work with unheard-of companies, and asking SPSRs to return later. CONCLUSIONS: The GP-pharmaceutical sales representative interaction that centres on profit-maximisation is complex as offers to engage in prescribing for mutual financial benefit are not taken up immediately. The SPSR method helps understand the extent of distortion of practices impacted by incentivisation. Such an understanding can support the development of strategies to control unethical behaviours.

Target product profiles: tests for tuberculosis treatment monitoring and optimization.

The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment. The development of the target product profiles was informed by a stakeholder survey, a cost-effectiveness analysis and a patient-care pathway analysis. Additional feedback from stakeholders was obtained by means of a Delphi-like process, a technical consultation and a call for public comment on a draft document. A scientific development group agreed on the final targets in a consensus meeting. For characteristics rated of highest importance, the document lists: (i) high diagnostic accuracy (sensitivity and specificity); (ii) time to result of optimally ≤ 2 hours and no more than 1 day; (iii) required sample type to be minimally invasive, easily obtainable, such as urine, breath, or capillary blood, or a respiratory sample that goes beyond sputum; (iv) ideally the test could be placed at a peripheral-level health facility without a laboratory; and (v) the test should be affordable to low- and middle-income countries, and allow wide and equitable access and scale-up. Use of these target product profiles should facilitate the development of new tuberculosis treatment monitoring and optimization tests that are accurate and accessible for all people being treated for tuberculosis.

L'Organisation mondiale de la santé a élaboré des profils de produits cibles contenant des cibles minimales et optimales pour les caractéristiques principales des essais destinés au suivi et à l'optimisation du traitement de la tuberculose. L'optimisation du traitement de la tuberculose fait référence à l'instauration d'un régime de traitement efficace de la tuberculose ou à l'adoption d'un tel régime, avec une probabilité élevée d'obtenir de bons résultats thérapeutiques. Les profils de produits cibles couvrent également les essais de guérison effectués à l'issue du traitement. Les profils de produits cibles ont été élaborés sur la base d'un sondage auprès des parties prenantes, d'une analyse coût-efficacité et d'une analyse du parcours de soins du patient. Des retours supplémentaires des parties prenantes ont été obtenus au moyen d'un processus créé selon la méthode Delphi, d'une consultation technique et d'un appel à commentaires publics sur un projet de document. Un groupe d'élaboration scientifique s'est mis d'accord sur les objectifs finaux lors d'une réunion de concertation. En ce qui concerne les caractéristiques jugées les plus importantes, le document énumère ce qui suit: (i) une grande précision diagnostique (sensibilité et spécificité); (ii) un délai idéal d'obtention des résultats ≤ 2 heures et au maximum de 1 jour; (iii) le type d'échantillon requis doit être peu invasif et facile à obtenir, comme l'urine, l'haleine ou le sang capillaire, ou bien un échantillon respiratoire au-delà des expectorations; (iv) idéalement, l'essai pourrait avoir lieu dans un établissement de santé périphérique sans laboratoire ; et (v) l'essai devrait être abordable pour les pays à revenu faible et intermédiaire et permettre un accès large et équitable ainsi qu'une mise à l'échelle. L'utilisation de ces profils de produits cibles devrait faciliter la mise au point de nouveaux essais de surveillance et d'optimisation du traitement de la tuberculose qui soient précis et accessibles à toutes les personnes suivant un traitement pour la tuberculose.

La Organización Mundial de la Salud ha elaborado perfiles de productos objetivo que contienen objetivos mínimos y óptimos para las características principales de las pruebas de seguimiento y optimización del tratamiento de la tuberculosis. La optimización del tratamiento de la tuberculosis consiste en iniciar o cambiar a un régimen eficaz de tratamiento de la tuberculosis que ofrezca una alta probabilidad de un buen resultado terapéutico. Los perfiles de productos objetivo también abarcan las pruebas de curación realizadas al final del tratamiento. La elaboración de los perfiles de los productos objetivo se basó en una encuesta a las partes interesadas, un análisis de rentabilidad y un análisis de la vía de atención al paciente. Se obtuvo información adicional de las partes interesadas mediante un proceso tipo Delphi, una consulta técnica y una convocatoria de comentarios públicos sobre un borrador del documento. Un grupo de desarrollo científico acordó los objetivos finales en una reunión de consenso. Para las características clasificadas de mayor importancia, el documento enumera: (i) alta precisión diagnóstica (sensibilidad y especificidad); (ii) tiempo hasta el resultado de óptimamente ≤ 2 horas y no más de 1 día; (iii) el tipo de muestra requerida debe ser mínimamente invasiva, fácil de obtener, como orina, aliento o sangre capilar, o una muestra respiratoria que vaya más allá del esputo; (iv) idealmente la prueba podría realizarse en un centro sanitario periférico sin laboratorio; y (v) la prueba debe ser asequible para los países de ingresos bajos y medios y permitir un acceso amplio y equitativo y su expansión. El uso de estos perfiles de producto objetivo debería facilitar el desarrollo de pruebas nuevas de seguimiento y optimización del tratamiento de la tuberculosis que sean precisas y accesibles para todas las personas que reciben tratamiento antituberculoso.

Cumulative antimicrobial susceptibilities for respiratory clinical isolates of Mycobacterium avium Complex, Mycobacterium kansasii, and Mycobacterium abscessus from Pakistan 2018 to 2022.

Background: Nontuberculous mycobacteria (NTM) are increasingly identified as causes of protracted pulmonary infections. Antibiotic susceptibility testing requires microdilution methods, which are often unavailable in laboratories in resource-poor settings. We report cumulative antibiograms for the most frequently isolated clinical pulmonary NTM from Pakistan to inform empiric antibiotic management of initial NTM infections. Methods: We analyzed data from 2018 to 2022 for the most frequently isolated and clinically relevant NTM isolated from respiratory specimens, i.e., Mycobacterium avium complex (MAC), Mycobacterium abscessus group (MAG), and Mycobacterium kansasii (MK). Antibiograms were developed using the Clinical Laboratory Standards Institute's M39ED5 standard. Percentage susceptibilities and 95% confidence intervals (CI) were calculated. Results: Over 4 years, 529 NTM, comprising 209 MAC, 249 MAG, and 71 MK were analyzed. For MAC and MAG, where clarithromycin (CLR)-based regimens are recommended, CLR was active for 94.8% (95% CI 91.3-96.9), and 77.5% (95% CI 71.4-82.7) isolates, respectively. Combination regimens comprising 3 active drugs CLR + linezolid (LZD) + moxifloxacin for MAC and CLR + LZD + Amikacin for MAG had 98.4% (95% CI 95.9-99.4) and 68.9% (95% CI 62.3-74.8) coverage for pulmonary disease, respectively. For MK, 91.5% (95% CI 82.8-96.1) isolates were susceptible to rifampin (RIF), with a combination of RIF + CLR covering 88.7% (95% CI 79.3-94.2) of MK pulmonary infections, respectively. Conclusions: These data can inform empiric treatment guidance for the most common NTM pulmonary infections, i.e., for MAC, MAG, and MK disease in Pakistan.

Sequential viral introductions and spread of BA.1 across Pakistan provinces during the Omicron wave.

BACKGROUND: COVID-19 waves caused by specific SARS-CoV-2 variants have occurred globally at different times. We focused on Omicron variants to understand the genomic diversity and phylogenetic relatedness of SARS-CoV-2 strains in various regions of Pakistan. METHODS: We studied 276,525 COVID-19 cases and 1,031 genomes sequenced from December 2021 to August 2022. Sequences were analyzed and visualized using phylogenetic trees. RESULTS: The highest case numbers and deaths were recorded in Sindh and Punjab, the most populous provinces in Pakistan. Omicron variants comprised 93% of all genomes, with BA.2 (32.6%) and BA.5 (38.4%) predominating. The first Omicron wave was associated with the sequential identification of BA.1 in Sindh, then Islamabad Capital Territory, Punjab, Khyber Pakhtunkhwa (KP), Azad Jammu Kashmir (AJK), Gilgit-Baltistan (GB) and Balochistan. Phylogenetic analysis revealed Sindh to be the source of BA.1 and BA.2 introductions into Punjab and Balochistan during early 2022. BA.4 was first introduced in AJK and BA.5 in Punjab. Most recent common ancestor (MRCA) analysis revealed relatedness between the earliest BA.1 genome from Sindh with Balochistan, AJK, Punjab and ICT, and that of first BA.1 from Punjab with strains from KPK and GB. CONCLUSIONS: Phylogenetic analysis provides insights into the introduction and transmission dynamics of the Omicron variant in Pakistan, identifying Sindh as a hotspot for viral dissemination. Such data linked with public health efforts can help limit surges of new infections.

Incentivisation practices and their influence on physicians' prescriptions: A qualitative analysis of practice and policy in Pakistan.

Focus on profit-generating enterprise in healthcare can create conflicts of interest that adversely impact prescribing and pricing of medicines. Although a global challenge, addressing the impacts on quality of care is particularly difficult in countries where the pharmaceutical industry and physician lobby is strong relative to regulatory institutions. Our study characterises the range of incentives exchanged between the pharmaceutical industry and physicians, and investigates the differences between incentivisation practices and policies in Pakistan. In this mixed methods study, we first thematically analysed semi-structured interviews with 28 purposively selected for-profit primary-care physicians and 13 medical sales representatives from pharmaceutical companies working across Pakistan's largest city, Karachi. We then conducted a content analysis of policies on ethical practice issued by two regulatory bodies responsible in Pakistan, and the World Health Organization. This enabled a systematic comparison of incentivisation practices with what is considered 'prohibitive' or 'permissive' in policy. Our findings demonstrate that incentivisation of physicians to meet pharmaceutical sales targets is the norm, and that both parties play in the symbiotic physician-pharma incentivisation dynamics. Further, we were able to categorise the types of incentive exchanged into one of five categories: financial, material, professional or educational, social or recreational, and familial. Our comparison of incentivisation practices with policies revealed three reasons for such widespread incentivisation linked to sales targets: first, some clear policies were being ignored by physicians; second, there are ambiguous or contradictory policies with respect to specific incentive types; and third, numerous incentive types are unaddressed by existing policies, such as pharmaceutical companies paying for private clinic renovations. There is a need for policies to be clarified and updated, and to build buy-in for policy enforcement from pharmaceutical companies and physicians, such that transgressions on target-driven prescribing are seen to be unethical.

Whole-genome sequencing reveals genotypic resistance in phenotypically susceptible Mycobacterium tuberculosis clinical isolates.

Background: Whole-genome sequencing (WGS) data of Mycobacterium tuberculosis (MTB) complex strains have revealed insights about genetic variants associated with drug resistance (DR). Rapid genome-based diagnostics are being sought for specific and sensitive identification of DR; however, correct prediction of resistance genotypes requires both informatics tools and understanding of available evidence. We analyzed WGS datasets from phenotypically susceptible MTB strains using MTB resistance identification software. Methods: WGS data for 1526 MTB isolates classified as phenotypically drug susceptible were downloaded from the ReSeqTB database. The TB-Profiler software was used to call Single Nucleotide Variants (SNV) associated with resistance to rifampicin (RIF), isoniazid (INH), ethambutol (EMB), pyrazinamide, fluoroquinolone (FLQ), streptomycin (STR), and aminoglycosides. The SNV were further matched against the 2021 World Health Organization (WHO) catalogue of resistance mutations. Results: Genome analysis of 1526 MTB strains susceptible to first-line drugs revealed 39 SNV associated with DR to be present in across 14 genes in 5.9% (n = 90) isolates. Further interpretation of SNV based on the WHO catalog of mutations revealed resistance that 21 (1.4%) MTB isolates were resistant to first-line (4 to RIF, 14 to INH, 3 to EMB) drugs. While, 36 (2.6%) isolates were resistant to second-line (19 to STR, 14 to FLQ, and three to capreomycin) agents. The most frequent predictive SNV were; rpoB Ser450 Leu for RIF; katG Ser315Thr, inhA Ser94Ala, fabG1-15C >T (for INH); gyrA Asp94Gly for FLQ; embB Met306 Leu for EMB; rpsL Lys43Arg for STR; and tlyA Asn236 Lys for Capreomycin. Conclusions: Our study highlights the value of WGS-based sequence data for identifying resistance in MTB. It also shows how MTB strains may be misclassified simply on phenotypic drug susceptibility testing, and that correct genome interpretation is key for correct interpretation of resistance genotypes that can be used to guide clinical treatment.

Laboratory service relocation: experience and lessons learned from relocating a biosafety level-3 clinical mycobacteriology service to a new facility.

Objectives: We recount our experiences of relocating an active mycobacteriology reference level service in Karachi, Pakistan, from an older accredited biosafety level-3 facility to a newly constructed and environmentally validated facility. Methods: The service relocation planning, execution, and verification stages are described in detail. Results: Lessons learned from our experience include establishing a service transfer plan, including relevant service staff, obtaining their buy-in on the plan, arranging backup service facilities or liaisons for the execution phase, and ensuring viable backup arrangements for troubleshooting during the verification phase of services in the new facility. Careful planning and inclusion of all stakeholders are critical to avoid service interruptions. Conclusions: This narrative is expected to support other laboratorians, scientists, and clinicians providing laboratory services to large population sectors who are looking to move their services to a new location while continuing to offer said services in a proficient and reliable manner.

Ceftriaxone resistant Salmonella enterica serovar Paratyphi A identified in a case of enteric fever: first case report from Pakistan.

BACKGROUND: Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global burden of 14.3 million cases. Cases of enteric fever or paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A (S. Para A) have been found to rise in many endemic and non-endemic countries. Drug resistance is relatively uncommon in S. Para A. Here we report a case of paratyphoid fever caused by ceftriaxone resistant S. Para A from Pakistan. CASE PRESENTATION: A 29-year-old female presented with a history of fever, headache, and shivering. Her blood culture revealed a S. Para A isolate (S7), which was resistant to ceftriaxone, cefixime, ampicillin and ciprofloxacin. She was prescribed oral Azithromycin for 10 days, which resulted in resolution of her symptoms. Two other isolates of S. Para A (S1 and S4), resistant to fluoroquinolone were also selected for comparison. DST and whole genome sequencing was performed for all three isolates. Sequence analysis was performed for identification of drug resistance and phylogeny. Whole Genome Sequencing (WGS) of S7 revealed the presence of plasmids, IncX4 and IncFIB(K). blaCTX-M-15 and qnrS1 genes were found on IncFIB(K). The gyrA S83F mutation conferring fluoroquinolone resistance was also found present. Multi-locus sequence typing (MLST) showed the S7 isolate to belong to ST129. S1 and S4 had the gyrA S83Y and S83F mutations respectively. CONCLUSIONS: We highlight the occurrence of plasmid-mediated ceftriaxone resistant strain of S. Para A. This is of significance as ceftriaxone is commonly used to treat paratyphoid fever and resistance in S. Para A is not known. Continuous epidemiological surveillance is required to monitor the transmission and spread of antimicrobial resistance (AMR) among Typhoidal Salmonellae. This will guide treatment options and preventive measures including the need for vaccination against S. Para A in the region.

Socioecological factors linked with pharmaceutical incentive-driven prescribing in Pakistan.

Pharmaceutical marketing through financial incentivisation to general practitioners (GPs) is a poorly studied health system problem in Pakistan. Pharmaceutical incentivisation is seen to be distorting GPs prescribing behaviour that can compromise the health and well-being of patients. We draw on a conceptual framework outlined in the ecological system theory to identify multiple factors linked with pharmaceutical incentivisation to GPs in Pakistan. We conducted qualitative interviews with 28 policy actors to seek their views on the health system dynamics, how they sustain pharmaceutical incentivisation and their effect on the quality of care. Our analysis revealed four interlinked factors operating at different levels and how they collectively contribute to pharmaceutical incentivisation. In addition to influences such as the increasing family needs and peers' financial success, sometimes GPs may naturally be inclined to maximise incomes by engaging in pharmaceutical incentivisation. On other hand, the pharmaceutical market dynamics that involve that competition underpinned by a profit-maximisation mindset enable pharmaceutical companies to meet GPs' desires/needs in return for prescribing their products. Inadequate monitoring and health regulations may further permit the pharmaceutical industry and GPs to sustain the incentive-driven relationship. Our findings have important implications for potential health reforms such as introducing regulatory controls, and appropriate monitoring and regulation of the private health sector, required to address pharmaceutical incentivisation to GPs.

The Landscape of Stem Cell Research in Pakistan.

Objectives: The present study is a scoping review of the progress of the field of stem cell research (SCR) in Pakistan in the last two decades. METHODS: Data was extracted from electronic search engines, international clinical trial registry platforms, and PubMed and presented in tabular and graphical form. RESULTS: China, India and Iran are investing heavily in SCR. In Pakistan, reasonable growth in terms of the number of publications is observed in this area, however, clinical translation of the field does not demonstrate any considerable progress. The Government of Pakistan has developed the regulatory framework and initiated preliminary policymaking, adopting rules from international regulatory agencies like World Health Organization (WHO) and Federal Drug Authority (FDA), however, further clarity and policymaking are needed to address the growing trend of stem cell tourism in the country. CONCLUSIONS: The field of SCR is still in its infancy in Pakistan, and needs improvement; scientists, academia, policymakers, and funding agencies must come together to foster high-impact stem cell research in the country. This will aid in elevating the economic burden of many incurable diseases in the country. The outcomes of this study will be helpful for policymakers in their decision-making process.

The healthcare field as a marketplace: general practitioners, pharmaceutical companies, and profit-led prescribing in Pakistan.

Incentivisation of general practitioners (GPs) by pharmaceutical companies is thought to affect prescribing practices, often not in patients' interest. Using a Bourdieusian lens, we examine the socially structured conditions that underpin exchanges between pharmaceutical companies and GPs in Pakistan. The analysis of qualitative interviews with 28 GPs and 13 pharmaceutical sales representatives (PSRs) shows that GPs, through prescribing medicines, met pharmaceutical sales targets in exchange for various incentives. We argue that these practices can be given meaning through the concept of 'field' - a social space in which GPs, PSRs, and pharmacists were hierarchically positioned, with their unique capacities, to enable healthcare provision. However, structural forces like the intense competition between pharmaceutical companies, the presence of unqualified healthcare providers in the healthcare market, and a lack of regulation by the state institutions produced a context that enabled pharmaceutical companies and GPs to use the healthcare field, also, as space to maximise profits. GPs believed the effort to maximise incomes and meet socially desired standards were two key factors that encouraged profit-led prescribing. We conclude that understanding the healthcare field is an important step toward developing governance practices that can address profit-led prescribing.

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

Impact of a multifaceted intervention on physicians' knowledge, attitudes and practices in relation to pharmaceutical incentivisation: protocol for a randomised control trial.

INTRODUCTION: In settings where the private sector constitutes a larger part of the health system, profit-gathering can take primacy over patients' well-being. In their interactions with pharmaceutical companies, private general practitioners (GPs) can experience the conflict of interest (COI), a situation whereby the impartiality of GPs' professional decision making may be influenced by secondary interests such as financial gains from prescribing specific pharmaceutical brands. METHODS AND ANALYSIS: This study is a randomised controlled trial to assess the impact of a multifaceted intervention on GPs' medical practice. The study sample consists of 419 registered GPs who own/work in private clinics and will be randomly assigned to intervention and control groups. The intervention group GPs will be exposed to emotive and educational seminars on medical ethics, whereas control group GPs will be given seminars on general medical topics. The primary outcome measure will be GPs' prescribing practices, whereas the secondary outcome measures will be their knowledge and attitudes regarding COI that arises from pharmaceutical incentivisation. In addition to a novel standardised pharmaceutical representatives (SPSR) method, in which field researchers will simulate pharmaceutical marketing with GPs, presurvey and postsurvey, and qualitative interviewing will be performed to collect data on GPs' knowledge, attitudes and practices in relation to COI linked with pharmaceutical incentives. Univariate and multivariate statistical analyses will be performed to measure a change in GPs' knowledge, attitudes and practices, while qualitative analysis will add to our understanding of the quantitative SPSR data. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Pakistan National Bioethics Committee (# 4-87/NBC-582/21/1364), the Aga Khan University (# 2020-4759-1129) and the London School of Hygiene and Tropical Medicine (# 26506). We will release results within 6-9 months of the study's completion. TRIAL REGISTRATION NUMBER: ISRCTN12294839.

Exploring stakeholders' experiences and perceptions regarding barriers to effective surveillance of communicable diseases in a rural district of Pakistan: a qualitative study.

OBJECTIVE: To explore the experiences and perceptions of health system stakeholders of a rural district of Sindh, Pakistan regarding the barriers to effective surveillance of communicable diseases. DESIGN: This qualitative descriptive exploratory design comprised in-depth interviews. Both inductive and deductive thematic analysis was applied to identify key themes from the data. SETTINGS: The study was conducted in public sector healthcare facilities and the district health office of the rural district of Thatta, in Sindh province, Pakistan. PARTICIPANTS: Fifteen healthcare managers and healthcare providers working in the eight public sector primary and secondary healthcare facilities were interviewed using an open-ended in-depth interview guide. RESULTS: Key themes that emerged from the data were: poor governance and absence of surveillance policy framework; fragmentation in the health system leading to lack of uniform reporting; inadequate (human) resources that weakened the infrastructure for disease surveillance; hospital-based reporting of cases that led to a predominantly passive surveillance system; paper-based surveillance system as the key determinant of delayed reporting; non-utilisation of surveillance data for decision making; absence of local laboratory capacity to complement the detection of disease outbreaks and lack of private sector integration in disease surveillance. CONCLUSIONS: Poor governance and lack of policy framework were perceived to be responsible for weak surveillance infrastructure. Resource deficiencies including inadequate human resource, paper-based reporting and the absence of local laboratory capacity were considered to result in delayed, poor quality and incomplete reporting. The lack of private sector engagement was identified as a major gap.

Comparative Analysis of Commercially Available Typhoid Point-of-Care Tests: Results of a Prospective and Hybrid Retrospective Multicenter Diagnostic Accuracy Study in Kenya and Pakistan.

Blood and bone marrow cultures are considered the gold standard for the diagnosis of typhoid, but these methods require infrastructure and skilled staff that are not always available in low- and middle-income countries where typhoid is endemic. The objective of the study is to evaluate the sensitivity and specificity of nine commercially available Salmonella Typhi rapid diagnostic tests (RDTs) using blood culture as a reference standard in a multicenter study. This was a prospective and retrospective multicenter diagnostic accuracy study conducted in two geographically distant areas where typhoid is endemic (Pakistan and Kenya; NCT04801602). Nine RDTs were evaluated, including the Widal test. Point estimates for sensitivity and specificity were calculated using the Wilson method. Latent class analyses were performed using R to address the imperfect gold standard. A total of 531 serum samples were evaluated (264 blood culture positive; 267 blood culture negative). The sensitivity of RDTs varied widely (range, 0 to 78.8%), with the best overall performance shown by Enterocheck WB (72.7% sensitivity, 86.5% specificity). In latent class modeling, CTK IgG was found to have the highest sensitivity (79.1%), while the highest overall accuracy was observed with Enterocheck (73.8% sensitivity, 94.5% specificity). All commercially available Salmonella Typhi RDTs evaluated in the study had sensitivity and specificity values that fell below the required levels to be recommended for an accurate diagnosis. There were minimal differences in RDT performances between regions of endemicity. These findings highlight the clear need for new and more-accurate Salmonella Typhi tests.