Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort.

BACKGROUND: Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. OBJECTIVES: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. METHODS: Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. RESULTS: Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. CONCLUSIONS: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.

Focused Ultrasound Thalamotomy: Correlation of Postoperative Imaging with Neuropathological Findings.

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson's disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including central hemorrhagic necrosis with surrounding cytotoxic edema and a rim of mostly unaffected vasogenic edema with some reactive and reparative processes. Overall, this case demonstrates the correlation of postoperative imaging findings with the subacute neuropathological findings after MRgFUS for PD.

Girl Champ in eSwatini: A Strategic Marketing Campaign to Promote Demand for Sexual and Reproductive Health Services Among Young Women.

Efforts to engage adolescent girls and young women (AGYW) in HIV services have struggled, in part, due to limited awareness of services and stigma. Strategic marketing is a promising approach, but the impact on youth behavior change is unclear. We report findings from a mixed methods evaluation of the Girl Champ campaign, designed to generate demand for sexual and reproductive services among AGYW, and piloted in three clinics in the Manzini region of eSwatini. We analyzed and integrated data from longitudinal, clinic-level databases on health service utilization among AGYW before and after the pilot, qualitative interviews with stakeholders responsible for the implementation of the pilot, and participant feedback surveys from attendees of Girl Champ events. Girl Champ was well received by most stakeholders based on event attendance and participant feedback, and associated with longitudinal improvements in demand for HIV services. Findings can inform future HIV demand creation interventions for youth.

Title: Expansion of a national differentiated service delivery model to support people living with HIV and other chronic conditions in South Africa: a descriptive analysis.

BACKGROUND: South Africa is home to 7.7 million people living with HIV and supports the largest antiretroviral therapy (ART) program worldwide. Despite global investment in HIV service delivery and the parallel challenge of non-communicable diseases (NCDs), there are few examples of integrated programs addressing both HIV and NCDs through differentiated service delivery. In 2014, the National Department of Health (NDoH) of South Africa launched the Central Chronic Medicines Dispensing and Distribution (CCMDD) program to provide patients who have chronic diseases, including HIV, with alternative access to medications via community-based pick-up points. This study describes the expansion of CCMDD toward national scale. METHODS: Yale monitors CCMDD expansion as part of its mixed methods evaluation of Project Last Mile, a national technical support partner for CCMDD since 2016. From March 2016 through October 2019, cumulative weekly data on CCMDD uptake [patients enrolled, facilities registered, pick-up points contracted], type of medication provided [ART only; NCD only; and ART-NCD] and collection sites preferred by patients [external pick-up points; adherence/outreach clubs; or facility-based fast lanes], were extracted for descriptive, longitudinal analysis. RESULTS: As of October 2019, 3,436 health facilities were registered with CCMDD across 46 health districts (88 % of South Africa's districts), and 2,037 external pick-up points had been contracted by the NDoH. A total of 2,069,039 patients were actively serviced through CCMDD, a significant increase since 2018 (p < 0.001), including 76 % collecting ART [64 % ART only, 12 % ART plus NCD/comorbidities] and 479,120 [24 %] collecting medications for chronic diseases only. Further, 734,005 (35 %) of patients were collecting from contracted, external pick-up points, a 73 % increase in patient volume from 2018. DISCUSSION: This longitudinal description of CCMDD provides an example of growth of a national differentiated service delivery model that integrates management of HIV and noncommunicable diseases. This study demonstrates the success of the program in engaging patients irrespective of their chronic condition, which bodes well for the potential of the program to address the rising burden of both HIV and NCDs in South Africa. CONCLUSIONS: The CCMDD program expansion signals the potential for a differentiated service delivery strategy in resource-limited settings that can be agnostic of the patients chronic disease condition.

Pater Knows Best: Withdrawal of Medical Treatment from Infants in Scotland.

The cases of Charlie Gard and Alfie Evans placed the withdrawal of treatment from terminally ill infants at the forefront of medical law and ethics. In the medico-legal context, Scottish court procedures materially differ from those in England. This article considers these differences in light of the possibility that a similar case might soon be called before the Scottish courts. The Court of Session would then be required to consider whether to utilise its parens patriae jurisdiction to consent to the withdrawal of treatment as if it were the parent of the infant. The operation of this jurisdiction is such that the outcome of any Scottish case cannot be said to be certain, as the Scottish courts are bound to pay more heed to parental autonomy than their English counterparts do.

Levels of resilience and delivery of HIV care in response to urban violence and crime.

AIMS: To understand the impact of urban violence and crime on HIV care delivery. BACKGROUND: Urban violence and crime can put pressure on the healthcare system and on nursing staff. Whilst there is research about the impact this has at the individual level, there is less research that places this in the context of the overall social eco-system. DESIGN: A qualitative design using inductive thematic analysis. METHODS: Between July 2016 - February 2017, we conducted in-depth interviews with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa. RESULTS: The effects of crime and violence were evident at multiple levels resulting in participants feeling "safe and unsafe" in a context where people view crime as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community, and organizational levels and enabled continued delivery of HIV care. CONCLUSION: The findings demonstrate the potential role of resilience in the social eco-health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism. IMPACT: This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco-system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime.

Harnessing citizen science through mobile phone technology to screen for immunohistochemical biomarkers in bladder cancer.

BACKGROUND: Immunohistochemistry (IHC) is often used in personalisation of cancer treatments. Analysis of large data sets to uncover predictive biomarkers by specialists can be enormously time-consuming. Here we investigated crowdsourcing as a means of reliably analysing immunostained cancer samples to discover biomarkers predictive of cancer survival. METHODS: We crowdsourced the analysis of bladder cancer TMA core samples through the smartphone app 'Reverse the Odds'. Scores from members of the public were pooled and compared to a gold standard set scored by appropriate specialists. We also used crowdsourced scores to assess associations with disease-specific survival. RESULTS: Data were collected over 721 days, with 4,744,339 classifications performed. The average time per classification was approximately 15 s, with approximately 20,000 h total non-gaming time contributed. The correlation between crowdsourced and expert H-scores (staining intensity × proportion) varied from 0.65 to 0.92 across the markers tested, with six of 10 correlation coefficients at least 0.80. At least two markers (MRE11 and CK20) were significantly associated with survival in patients with bladder cancer, and a further three markers showed results warranting expert follow-up. CONCLUSIONS: Crowdsourcing through a smartphone app has the potential to accurately screen IHC data and greatly increase the speed of biomarker discovery.

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays.

BACKGROUND: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing - enlisting help from the public - is a sufficiently accurate method to score such samples. METHODS: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers - bladder/ki67, lung/EGFR, and oesophageal/CD8 - to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants' accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. RESULTS: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). CONCLUSIONS: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains.

How electronic health records can unmask the hidden value of PAs.

The Fee for Value (FFV) Task Force, a subgroup of the American Academy of PAs' Research and Strategic Initiatives Commission, has examined tools and mechanisms aimed at better clarifying the volume and value of PA work and how that work contributes to improving access to high-quality care. Establishing the value of PAs has been a challenging task for many healthcare providers. Often, PA value has been defined by their clinical productivity, without any clear direction as to what constitutes value versus productivity. The objective of this article is to unmask the value of PAs through the role of electronic health records and highlight PAs' ability to produce services that are value-oriented and quantifiably productive.

HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa.

The aim of this investigation was to identify factors associated with HIV transmission risk behavior among HIV-positive women and men receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. Across 16 clinics, 1,890 HIV+ patients on ART completed a risk-focused audio computer-assisted self-interview upon enrolling in a prevention-with-positives intervention trial. Results demonstrated that 62 % of HIV-positive patients' recent unprotected sexual acts involved HIV-negative or HIV status unknown partners. For HIV-positive women, multivariable correlates of unprotected sex with HIV-negative or HIV status unknown partners were indicative of poor HIV prevention-related information and of sexual partnership-associated behavioral skills barriers. For HIV-positive men, multivariable correlates represented motivational barriers, characterized by negative condom attitudes and the experience of depressive symptomatology, as well as possible underlying information deficits. Findings suggest that interventions addressing gender-specific and culturally-relevant information, motivation, and behavioral skills barriers could help reduce HIV transmission risk behavior among HIV-positive South Africans.

Information, motivation, and behavioral skills for early pre-ART engagement in HIV care among patients entering clinical care in KwaZulu-Natal, South Africa.

Little is known regarding factors implicated in early engagement and retention in HIV care among individuals not yet eligible for antiretroviral therapy (pre-ART) in sub-Saharan Africa. Identifying such factors is critical for supporting retention in pre-ART clinical care to ensure timely ART initiation and optimize long-term health outcomes. We assessed patients' pre-ART HIV care-related information, motivation, and behavioral skills among newly diagnosed ART-ineligible patients, initiating care in KwaZulu-Natal, South Africa. The survey was interviewer-administered to eligible patients, who were aged 18 years or older, newly entering care (diagnosed within the last six-months), and ineligible for ART (CD4 count > 200 cells/mm(3)) in one of four primary care clinical sites. Self-reported information, motivation, and behavioral skills specific to retention in pre-ART HIV-care were characterized by categorizing responses into those reflecting potential strengths and those reflective of potential deficits. Information, motivation, and behavioral skills deficits sufficiently prevalent in the overall sample (i.e.,≥30% prevalent) were identified as areas in need of specific attention through intervention efforts adapted to the clinic level. Gender-based differences were also evaluated. A total of 288 patients (75% female) completed structured interviews. Across the sample, eight information, eight motivation, and eight behavioral skills deficit areas were identified as sufficiently prevalent to warrant specific targeted attention. Gender differences did not emerge. The deficits in pre-ART HIV care-related information, motivation, and behavioral skills that were identified suggest that efforts to improve accurate information on immune function and HIV disease are needed, as is accurate information regarding HIV treatment and transmission risk prior to ART initiation. Additional efforts to facilitate the development of social support, including positive interactions with clinic staff and decreasing community-level stigma and to decrease structural and resource-depleting demands of HIV care may be particularly valuable to facilitate retention in pre-ART HIV care.

Assessing changes in adolescent girls' and young women's sexual and reproductive health service utilisation following a COVID-19 lockdown in eSwatini.

The effects of COVID-19-associated restrictions on youth sexual and reproductive health (SRH) care during the pandemic remain unclear, particularly in sub-Saharan Africa. This study uses interrupted time series analyses to assess changes in SRH care utilisation (including visits for HIV testing and treatment, family planning, and antenatal care) adolescent girls' and young women's (AGYW; aged 15-24 years old) in eSwatini following COVID-19 lockdown beginning in March 2020. SRH utilisation data from 32 clinics in the Manzini region that remained open throughout the 2020 COVID-19 period were extracted from eSwatini's electronic health record system. We tabulated and graphed monthly visits (both overall and by visit type) by AGYW during the two-year period between January 2019 and December 2020. Despite the March to September 2020 lockdown, we did not detect significant changes in monthly visit trends from 2019 to 2020. Our findings suggest little change to AGYW's SRH utilisation in eSwatini during the 2020 COVID-19 lockdown period.

Persuasive COVID-19 vaccination campaigns on Facebook and nationwide vaccination coverage in Ukraine, India, and Pakistan.

Social media platforms have a wide and influential reach, and as such provide an opportunity to increase vaccine uptake. To date, there is no large-scale, robust evidence on the offline effects of online messaging campaigns. We aimed to test whether pre-tested, persuasive messaging campaigns from UNICEF, disseminated on Facebook, influenced COVID-19 vaccine uptake in Ukraine, India, and Pakistan. In Ukraine, we deployed a stepped-wedge randomized controlled trial (RCT). Half of the 24 oblasts (provinces) received five weeks of the intervention, the other half ten weeks of the intervention. In India, an RCT with an augmented synthetic control was conducted in five states (Bihar, Chhattisgarh, Jharkhand, Madhya Pradesh, Rajasthan), whereby 40 out of 174 districts were randomized to receive six weeks of intervention. In Pakistan we deployed a pre-post design, whereby 25 city districts received six weeks of the intervention. Weekly COVID-19 vaccination data was sourced through government databases. Using Poisson regression models, the association between the intervention and vaccine uptake was estimated. In Ukraine we conducted a survey among Facebook users at three time points during the RCT, to ascertain vaccination intentions and trust in vaccines. The campaigns reached more than 110 million Facebook users and garnered 2.9 million clicks. In Ukraine, we found that the intervention did not affect oblast-level vaccination coverage (Relative Risk (RR): 0.93, 95% Confidence Interval (CI) 0.86-1.01). Similarly, in India and Pakistan we found no effect of our intervention (India: RR 0.85, 95% CI 0.70-1.04; Pakistan: RR 0.64, 95% CI 0.01-29.9). The survey among Facebook users in Ukraine showed that trust in vaccines and information sources was an important predictor of vaccination status and intention to get vaccinated. Our campaigns on Facebook had a wide reach, which did not translate in shifting behaviours. Timing and external events may have limited the effectiveness of our interventions.

The Evolution of Trust Within a Global Health Partnership With the Private Sector: An Inductive Framework.

BACKGROUND: Public-private partnerships (PPPs) in global health are increasingly common to support sustainable development and strengthen health systems in low- and middle-income countries. Since the release of the Sustainable Development Goals (SDGs) in 2015 culminating in a discrete goal "to revitalize the global partnership for sustainable development," public health scholars have sought to understand what makes PPPs successful in different contexts. While trust has long been identified as a key component of successful strategic alliances in the private sector, less is known about how trust emerges between public- and private- sector partners, particularly in global health. Therefore, we investigated how trust between partners evolved in the context of Project Last Mile (PLM), a global health partnership that translates the business acumen of The Coca-Cola Company to strengthen public health systems across Africa. METHODS: This study draws upon secondary analysis of qualitative data generated as part of the longitudinal, mixed-methods evaluation of PLM across country settings. Seventy-seven interviews with a purposeful sample of key stakeholders were conducted in Mozambique, South Africa and eSwatini between August 2016 and July 2018. Trained qualitative interviewers followed a standard discussion guide, and audio-recorded interviews with participants' consent. In this secondary analysis, we analyzed qualitative data to understand how trust between partners was cultivated across settings. RESULTS: We drew upon stakeholder experiences to inform an inductive framework for how trust develops over time. Our analysis revealed five domains that were foundational to building trust: (1) reputational context, (2) team composition, (3) tangible outputs, (4) shared values, and (5) effective communication. CONCLUSION: The framework may be useful for private and public sector entities seeking to establish and sustain trust within their global health partnerships.

Project Last Mile and the development of the Girl Champ brand in eSwatini: engaging the private sector to promote uptake of health services among adolescent girls and young women.

In eSwatini and across sub-Saharan Africa, adolescent girls and young women (AGYW) are at significantly higher risk of HIV infection and poorer sexual and reproductive health (SRH) than their male counterparts. AGYW demonstrate low demand for SRH services, further contributing to poor outcomes. Strategic marketing approaches, including those used by multinational corporations, have potential to support demand creation for SRH services among AGYW, but there is limited empirical evidence on the direct application of private-sector strategic marketing approaches in this context. Therefore, we examined how Project Last Mile worked with eSwatini's Ministry of Heath to translate strategic marketing approaches from the Coca-Cola system to attract AGYW to SRH services. We present qualitative market research using the ZMET® methodology with 12 young Swazi women (ages 15-24), which informed development of a highly branded communication strategy consistent with other successful gain-framing approaches. Qualitative in-depth interviews with 19 stakeholders revealed receptivity to the market research findings, and highlighted local ownership over the strategic marketing process and brand. These results can inform similar efforts to translate strategic marketing to support demand generation in pursuit of public health goals to reduce HIV risk and improve SRH.

AIDS, employment, and the direct threat defense: the burden of proof and the circuit court split.

This Note examines disability-related discrimination in light of the protections afforded by the Americans with Disabilities Act (ADA) and in the context of an HIV- or AIDS-infected employee. Under the ADA, an employer may legally fire a worker who poses a direct threat to the individuals around him or her. It is unclear, however, whether the burden of proving or disproving the claim that an individual is a direct threat lies with the employer or the employee. This Note analyzes the circuit split over which party bears the burden of proof under the direct threat standard in light of prospective HIV-related litigation.

Sexual risk behaviour among HIV-positive individuals in clinical care in urban KwaZulu-Natal, South Africa.

We assessed the incidence and predictors of unprotected sex among 152 HIV-positive patients in clinical care in KwaZulu-Natal, South Africa. Nearly 50% were sexually active; 30% of those reported unprotected sex. Alcohol use during sex, reporting forced sex, sex with a perceived HIV-positive partner, and sex with a casual partner predicted more unprotected sex, whereas HIV status disclosure was related to less unprotected sex. These findings highlight the need for linking HIV prevention and care in Africa.

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer.

BACKGROUND: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.