Time-Dependent Bacterial Contamination of a Surgical Suction Tip.

Background: No in vitro surgical study has evaluated the time-dependent contamination of surgical suction tips compared with controls. Our purpose was to determine the difference in suction tip bacterial contamination rates between suction-positive and suction-negative tips. Materials and Methods: A matched-pair analysis of the contamination of surgical suction tips over a six-hour period was performed in two clean operating rooms. One suction tip was connected to standard wall suction (suction-positive group), with a matched control tip not connected to wall suction (suction-negative group). At time zero and then at hourly intervals for six hours, the distal 3 cm of suction tips were removed, placed in nutrient broth for 48 hours, then plate cultured. One hundred tips were collected for each time interval. Results: Eighty-two of 700 (11.7%) suction tips had bacterial contamination. Sixty-three (18.0%) of 350 suction-positive tips were contaminated, with 19 (5.4%) of the 350 suction-negative tips contaminated (χ2 = 26.7, p < 0.001). Suction tip contamination was time-dependent with the first significant difference between groups occurring after two hours of continuous suction (χ2 = 4.0, p = 0.04). Contamination rate in the suction-positive group increased significantly after one hour compared with time-zero controls (χ2 = 7.1, p = 0.008). There was no significant difference in frequency of positive cultures over time in the suction-negative group compared with time-zero controls. Conclusions: This is the first controlled laboratory study suggesting a time-dependent increase in positive suction tip cultures. From our data, operating room staff should have an awareness that suction tips represent a potential source of bacterial concentration. We recommend that when not in use, suction tip valves be closed if this feature is available, that hosing be manipulated to cease suction when not needed, that suckers be disconnected from tubing, or that suckers be exchanged at frequent intervals. Doing so may reduce bacterial contamination on the suction tip.

Paralogue-selective degradation of the lysine acetyltransferase EP300.

The transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit non-redundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner. Mechanistic studies reveal that selective degradation cannot be predicted solely by target engagement or ternary complex formation, suggesting additional factors govern paralogue-specific degradation. MC-1 inhibits cell proliferation in a subset of cancer cell lines and provides a new tool to investigate the non-catalytic functions of EP300 and CREBBP. Our findings expand the repertoire of EP300/CREBBP-targeting chemical probes and offer insights into the determinants of selective degradation of highly homologous proteins.

Transiliac-Shortening Osteotomy to Treat Ischial Pressure Injury due to Fixed Pelvic Obliquity: A Case Report.

CASE: A 17-year-old adolescent boy with Gross Motor Function Classification System 5 cerebral palsy and neuromuscular scoliosis underwent posterior spinal fusion and segmental spinal instrumentation from T3 to the pelvis. He developed a right ischial pressure injury a few months postoperatively, which persisted despite nonoperative measures. He subsequently underwent an ipsilateral transiliac-shortening osteotomy 16 months after spinal surgery to treat his residual pelvic obliquity and the ischial pressure injury, which healed completely. At the 1-year follow-up visit, there were no further signs of pressure injury. CONCLUSION: This case report describes transiliac-shortening osteotomy as a viable treatment option for non-healing ischial pressure injuries secondary to fixed pelvic obliquity.

Implementation and Assessment of the HIV Enhanced Access Testing in the Emergency Department (HEATED) Program in Nairobi, Kenya: A Quasi-Experimental Prospective Study.

Background: Persons seeking emergency injury care are often from underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. Methods: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed using setting specific data and utilizes resource reorganization, services integration and HIV sensitization to promote ED-HTS. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and those never previously HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. Results: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR=1.31, 95% CI:1.21-1.43; p<0.001) with a 62.9% relative increase in HIV self-test kit provision. Among 605 patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR=11.2, 95%CI:6.9-18.1; p<0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR=13.8, 95%CI:5.5-28.7, p<0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16-weeks post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. Conclusions: The HEATED program increased ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons, already in contact with health systems.

The effect of surgical time on perioperative complications in adolescent idiopathic scoliosis cases. A propensity score analysis.

BACKGROUND: Posterior spinal instrumentation and fusion (PSIF) for adolescent idiopathic scoliosis (AIS) can be lengthy and complication-ridden. The aim of this study was to evaluate the effect of surgical time on perioperative complications in this procedure when controlling for confounding variables with propensity score analysis. METHODS: This was an IRB-approved review of electronic health records from 2010 to 2019 at a single tertiary care children's hospital. Patients undergoing PSIF were grouped into "short" (< 6 h) or "long" (≥ 6 h) surgical time groups. Outcome measures were estimated blood loss (EBL), cell saver transfusions, packed red blood cell (pRBC) transfusions, length of stay (LOS), intraoperative monitoring (IOM) alerts, hematocrit, ICU transfer, neurologic loss, surgical site infection, and 90-day readmissions. We controlled for age, sex, BMI, curve severity, number of segments fused, and surgeon factors. RESULTS: After propensity score matching there were 113 patients in each group. The short surgical time group had lower EBL (median 715, IQR 550-900 vs median 875, IQR 650-1100 cc; p < 0.001), received less cell saver blood (median 120, IQR 60-168 vs median 160, IQR 97-225 cc; p = 0.001), received less intraoperative pRBCs (median 0, IQR 0-0 vs median 0, IQR 0-320, p = 0.002), had shorter average LOS (4.8 ± 1.7 vs 5.4 ± 2.5 days; p = 0.039), and fewer IOM alerts (4.3% vs 18%, p = 0.003). CONCLUSIONS: Patients with shorter surgical times had less blood loss, received less transfused blood, had a shorter LOS, and fewer IOM alerts compared to patients with longer surgical times. Surgical times < 6 h may have safety and efficacy advantages over longer times. LEVEL OF EVIDENCE: III.

Pediatric Type I Open Both Bone Forearm Fractures: Predicting Failure of Nonoperative Management.

BACKGROUND: In recent years, nonoperative treatment of pediatric type I open both bone forearm fractures (OBBFFs) with bedside irrigation, antibiotics, closed reduction, and casting has yielded low infection rates. However, risk factors for failure of type I OBBFF closed reduction have not been well described. Our purpose was to describe management of patients with type I OBBFFs at our institution and determine what factors are associated with failure of closed reduction in this population. METHODS: This was a review of patients between 5 and 15 years of age who received initial nonoperative management for type I OBBFFs at one institution between 2015 and 2021. Primary outcome was success or failure of nonoperative management (defined as progression to surgical management). Secondary outcomes included infections, compartment syndromes, and neuropraxias. Other variables of interest were demographic information, prereduction and postreduction translation and angulation of the radius and ulna, cast index, and antibiotic administration. RESULTS: Sixty-one patients (67.7% male) with 62 type I OBBFFs were included in this study. Following initial nonoperative management, 55 injuries (88.7%) were successfully treated in casts, while the remaining 7 (11.3%) required surgical intervention following loss of acceptable reduction in cast. Median cast index (0.84, IQR 0.8 to 0.9 vs. 0.75, IQR 0.7-0.8, P=0.020) and postreduction radius translation on anteroposterior films (32.0%, IQR 17.0% to 40.0% vs. 5.0%, IQR 0.0% to 26.0%, P=0.020) were higher among those who failed nonoperative management. Multivariable logistic regression models identified increased odds of failure for every SD (0.7) increase in cast index (OR 3.78, P=0.023, 95% CI: 1.4-14.3) and 25% increase in postreduction radius translation on anteroposterior films (OR 7.39, P=0.044, 95% CI 1.2-70.4). No infections or compartment syndromes and 2 transient ulnar neuropraxias occurred. CONCLUSIONS: Closed reduction of type I OBBFFs was successful in 88.7% of cases. There were no infections after nonoperative management. Increases in cast index of 0.7 and postreduction radius translation on anteroposterior radiographs of 25% were associated with increased likelihood of failure, thus requiring surgery; age was not. LEVEL OF EVIDENCE: Level IV-retrospective comparative study.

Lack of Association of A1C With Postoperative Complications in Children With Type 1 or Type 2 Diabetes.

Not meeting recommended A1C targets may be associated with postoperative complications in adults, but there are no studies reporting on the relationship between preoperative A1C and postoperative complications in children with type 1 or type 2 diabetes. The objective of this study was to determine whether elevated A1C levels were associated with an increased incidence of postoperative complications in children with diabetes presenting for elective noncardiac surgery or diagnostic procedures. It found no such association, suggesting no need to delay elective surgery in children with diabetes until A1C is optimized.

2015-2021 Industry Payments to Pediatric Orthopaedic Surgeons: Analysis of Trends and Characteristics of Top-earning Surgeons.

BACKGROUND: Analysis of industry payments to pediatric orthopaedic surgeons last occurred in 2017. We investigated payments to pediatric orthopaedic surgeons from 2015 to 2021 to understand surgeon characteristics associated with increased industry payments. METHODS: Open Payments Database datasets from 2015 to 2021 were queried for nonresearch payments to pediatric orthopaedic surgeons. Annual aggregates and subcategories were recorded. For surgeons receiving payments in 2021, the Hirsch index (h-index), gender, and US census division were found using the Scopus database, Open Payments Database, and online hospital profiles, respectively. χ 2 , Fisher exact, Mann-Whitney U , and t tests were used to compare surgeons in the top 25%, 10%, and 5% payment percentiles to the bottom 75%, 90%, and 95%, respectively. RESULTS: Payments rose 125% from 2015 to 2021. Education, royalties, and faculty/speaker increased most, while travel/lodging, honoraria, charitable contributions, and ownership interest decreased. Only royalties increased from 2019 to 2021. In 2021, of 419 pediatric orthopaedic surgeons receiving industry payments, men received greater median aggregate payments than women ($379.03 vs. $186.96, P =0.047). There were no differences in gender proportions between the top 75% and bottom 25% ( P =0.054), top 10% and bottom 90% ( P =0.235), and top 5% and bottom 95% ( P =0.280) earning comparison groups. The h-index was weakly positively correlated with industry payments ( rs =0.203, P <0.001). Mean h-indices in the 75th ( P <0.001, 95% CI: 2.62-7.65), 90th ( P =0.001, 95% CI: 3.28-13.03), and 95th ( P =0.005, 95% CI: 4.25-21.11) percentiles were significantly higher. Proportions of surgeons from the Middle Atlantic and West South Central in the 90th ( P =0.025) and 95th percentiles ( P =0.033), respectively, were significantly lower compared to all other regions. A higher proportion of surgeons from the Pacific were placed in the 90th ( P =0.004) and 95th ( P =0.024) percentiles. CONCLUSIONS: Industry payments to pediatric orthopaedic surgeons rose from 2015 to 2021. Most categories fell from 2019 to 2021, which may be related to the SARS-CoV-19 pandemic. In 2021, though gender was not related to aggregate payment percentile, location in select US census divisions and h-index was. LEVEL OF EVIDENCE: Level II-Retrospective study.

Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. METHODS: Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. RESULTS: In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45-1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74-1.75). CONCLUSIONS: The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA's implementation with significant disruptions in FP care delivery during the trial. While SAIA's data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.

Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors.

The human acetyltransferase paralogues EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge. To address this gap, here we present a comparative study of drug-like EP300/CREBBP acetyltransferase inhibitors. First, we determine the biochemical and biological potencies of A-485, iP300w, and CPI-1612, highlighting the increased potencies of the latter two compounds at physiological acetyl-CoA concentrations. Cellular evaluation shows that inhibition of histone acetylation and cell growth closely aligns with the biochemical potencies of these molecules, consistent with an on-target mechanism. Finally, we demonstrate the utility of comparative pharmacology by using it to investigate the hypothesis that increased CoA synthesis caused by knockout of PANK4 can competitively antagonize the binding of EP300/CREBBP inhibitors and demonstrate proof-of-concept photorelease of a potent inhibitor molecule. Overall, our study demonstrates how knowledge of the relative inhibitor potency can guide the study of EP300/CREBBP-dependent mechanisms and suggests new approaches to target delivery, thus broadening the therapeutic window of these preclinical epigenetic drug candidates.

Chemoproteomics Yields a Selective Molecular Host for Acetyl-CoA.

Chemoproteomic profiling is a powerful approach to define the selectivity of small molecules and endogenous metabolites with the human proteome. In addition to mechanistic studies, proteome specificity profiling also has the potential to identify new scaffolds for biomolecular sensing. Here, we report a chemoproteomics-inspired strategy for selective sensing of acetyl-CoA. First, we use chemoproteomic capture experiments to validate the N-terminal acetyltransferase NAA50 as a protein capable of differentiating acetyl-CoA and CoA. A Nanoluc-NAA50 fusion protein retains this specificity and can be used to generate a bioluminescence resonance energy transfer (BRET) signal in the presence of a CoA-linked fluorophore. This enables the development of a ligand displacement assay in which CoA metabolites are detected via their ability to bind the Nanoluc-NAA50 protein "host" and compete binding of the CoA-linked fluorophore "guest". We demonstrate that the specificity of ligand displacement reflects the molecular recognition of the NAA50 host, while the window of dynamic sensing can be controlled by tuning the binding affinity of the CoA-linked fluorophore guest. Finally, we show that the method's specificity for acetyl-CoA can be harnessed for gain-of-signal optical detection of enzyme activity and quantification of acetyl-CoA from cellular samples. Overall, our studies demonstrate the potential of harnessing insights from chemoproteomics for molecular sensing and provide a foundation for future applications in target engagement and selective metabolite detection.

Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors.

The human acetyltransferase paralogs EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge. To address this gap, here we present a comparative study of drug-like EP300/CREBBP acetyltransferase inhibitors. First, we determine the biochemical and biological potencies of A-485, iP300w, and CPI-1612, highlighting the increased potency of the latter two compounds at physiological acetyl-CoA concentrations. Cellular evaluation shows that inhibition of histone acetylation and cell growth closely aligns with the biochemical potencies of these molecules, consistent with an on-target mechanism. Finally, we demonstrate the utility of comparative pharmacology by using it to investigate the hypothesis that increased CoA synthesis caused by knockout of PANK4 can competitively antagonize binding of EP300/CREBBP inhibitors and demonstrate proof-of-concept photorelease of a potent inhibitor molecule. Overall, our study demonstrates how knowledge of relative inhibitor potency can guide the study of EP300/CREBBP-dependent mechanisms and suggests new approaches to target delivery, thus broadening the therapeutic window of these preclinical epigenetic drug candidates.

Modeling the antidepressant treatment response to transcranial magnetic stimulation using an exponential decay function.

Recovery from depression often demonstrates a nonlinear pattern of treatment response, where the largest reduction in symptoms is observed early followed by smaller improvements. This study investigated whether this exponential pattern could model the antidepressant response to repetitive transcranial magnetic stimulation (TMS). Symptom ratings from 97 patients treated with TMS for depression were collected at baseline and after every five sessions. A nonlinear mixed-effects model was constructed using an exponential decay function. This model was also applied to group-level data from several published clinical trials of TMS for treatment-resistant depression. These nonlinear models were compared to corresponding linear models. In our clinical sample, response to TMS was well modeled with the exponential decay function, yielding significant estimates for all parameters and demonstrating superior fit compared to a linear model. Similarly, when applied to multiple studies comparing TMS modalities as well as to previously identified treatment response trajectories, the exponential decay models yielded consistently better fits compared to linear models. These results demonstrate that the antidepressant response to TMS follows a nonlinear pattern of improvement that is well modeled with an exponential decay function. This modeling offers a simple and useful framework to inform clinical decisions and future studies.

Fertility Desire and Associations with Condomless Sex, Antiretroviral Adherence, and Transmission Potential in a Cohort of Kenyan Women Living with HIV in Sero-discordant Relationships: A Mixed Methods Study.

For women living with HIV (WLH) in serodiscordant partnerships, decisions about childbearing can challenge condom use and antiretroviral adherence. In a prospective cohort of 148 WLH in serodiscordant partnerships, 58 (39%) wanted more children in the future but were not currently trying to conceive (fertility desire), and 32 (22%) were currently trying to become pregnant (fertility intent). Detection of prostate specific antigen (PSA) in vaginal secretions, a marker for recent condomless sex, was lowest in women with fertility desire and highest in women with fertility intent. Detectable viral load followed a similar pattern. Risk of HIV transmission, when condomless sex and PSA detection occurred concurrently, was three to fourfold higher at visits with fertility intent compared to visits with fertility desire. Qualitative interviews underscored the importance women place on childbearing and suggested that they had limited information about the role of antiretroviral therapy in reducing sexual HIV transmission.

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder: Prevention in the Context of New Trauma.

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that can result from experiencing a traumatic event. While a single index trauma can result in PTSD, patients often have additional traumatic events over the course of their lives. Despite this, little research to date has focused on prevention of PTSD recurrence following a novel traumatic experience. We present three cases of individuals with chronic PTSD who experienced an additional traumatic experience during treatment with transcranial magnetic stimulation (TMS) at VA Providence. Despite expectations to the contrary, TMS appeared to prevent a recurrence or worsening of their PTSD symptoms. We discuss possible neurobiological explanations for these outcomes and implications for possible use of TMS to prevent PTSD following trauma.

Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a signature injury of military conflicts and is prevalent in veterans with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Although therapeutic transcranial magnetic stimulation (TMS) can reduce symptoms of depression and PTSD, whether traumatic brain injury (TBI) affects TMS responsiveness is not yet known. We hypothesized mTBI would be associated with higher pretreatment symptom burden and poorer TMS response. MATERIALS AND METHODS: We investigated a registry of veterans (N = 770) who received TMS for depression across the US Veterans Affairs system. Of these, 665 (86.4%) had data on TBI and lifetime number of head injuries while 658 had complete data related to depression outcomes. Depression symptoms were assessed using the nine-item Patient Health Questionnaire and PTSD symptoms using the PTSD Checklist for DSM-5. Linear mixed effects models and t-tests evaluated whether head injuries predicted symptom severity before treatment, and how TBI status affected clinical TMS outcomes. RESULTS: Of the 658 veterans included, 337 (50.7%) reported previous mTBI, with a mean of three head injuries (range 1-20). TBI status did not predict depressive symptom severity or TMS-associated changes in depression (all p's > 0.1). TBI status was associated with a modest attenuation of TMS-associated improvement in PTSD (in patients with PTSD Checklist for DSM-5 scores > 33). There was no correlation between the number of head injuries and TMS response (p > 0.1). CONCLUSIONS: Contrary to our hypothesis, presence of mTBI did not meaningfully change TMS outcomes. Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness. Limitations include those inherent to retrospective registry studies and self-reporting. Although these findings are contrary to our hypotheses, they support the safety and effectiveness of TMS for MDD and PTSD in patients who have comorbid mTBI.

The cost of implementing the Systems Analysis and Improvement Approach for a cluster randomized trial integrating HIV testing into family planning services in Mombasa County, Kenya.

BACKGROUND: Although HIV testing in family planning (FP) clinics is a promising approach for engaging women in HIV treatment and prevention services, HIV testing rates are low in FP clinics in Kenya. In 2018, a cluster randomized trial was implemented in Mombasa, Kenya applying the Systems Analysis and Improvement Approach (SAIA) to integrate HIV testing into FP services (1K24HD088229-01). We estimated the incremental costs and explored cost drivers of the FP HIV SAIA implementation in Mombasa, Kenya. METHODS: We conducted a costing evaluation from the payer perspective for the FP HIV SAIA randomized control trial. We identified relevant activities for the intervention including start-up, training, research and FP HIV SAIA. We estimated activity time burden using a time-and motion study. We derived unit costs through staff interviews and programmatic budgets. We present cost estimates for two different scenarios: as-implemented including research and projected costs for a Ministry of Health-supported intervention. All costs are reported in 2018 USD. RESULTS: For an annual program output of 36,086 HIV tests administered to new FP clients, we estimated the total annual program cost to be $91,994 with an average cost per new FP client served of $2.55. Personnel and HIV rapid testing kits comprised 55% and 21% of programmatic costs, respectively. Assuming no changes to program outputs and with efficiency gains under the MOH scenario, the estimated cost per new FP client served decreased to $1.30 with a programmatic cost reduction of 49%. CONCLUSION: FP HIV SAIA is a low-cost and flexible implementation strategy for facilitating integrated delivery of HIV testing alongside FP services. Although cost implications of the FP HIV SAIA intervention must continue to be evaluated over time, these findings provide context-specific cost data useful for budget planning and decision-making regarding intervention delivery and expansion. TRIAL REGISTRATION: The trial was registered on December 15, 2016, with clinicaltrials.gov (NCT02994355).

A cross-sectional study of the prevalence, barriers, and facilitators of cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya. METHODS: Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening. RESULTS: A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2-6) with a median of 1 provider trained to perform screening (IQR 0-3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05-2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI 1.82-7.83). CONCLUSION: Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.

Assessing the sustainability of the Systems Analysis and Improvement Approach to increase HIV testing in family planning clinics in Mombasa, Kenya: results of a cluster randomized trial.

BACKGROUND: In Kenya, HIV incidence is highest among reproductive-age women. A key HIV mitigation strategy is the integration of HIV testing and counseling (HTC) into family planning services, but successful integration remains problematic. We conducted a cluster-randomized trial using the Systems Analysis and Improvement Approach (SAIA) to identify and address bottlenecks in HTC integration in family planning clinics in Mombasa County, Kenya. This trial (1) assessed the efficacy of this approach and (2) examined if SAIA could be sustainably incorporated into the Department of Health Services (DOHS) programmatic activities. In Stage 1, SAIA was effective at increasing HTC uptake. Here, we present Stage 2, which assessed if SAIA delivery would be sustained when implemented by the Mombasa County DOHS and if high HTC performance would continue to be observed. METHODS: Twenty-four family planning clinics in Mombasa County were randomized to either the SAIA implementation strategy or standard care. In Stage 1, the study staff conducted all study activities. In Stage 2, we transitioned SAIA implementation to DOHS staff and compared HTC in the intervention versus control clinics 1-year post-transition. Study staff provided training and minimal support to DOHS implementers and collected quarterly HTC outcome data. Interviews were conducted with family planning clinic staff to assess barriers and facilitators to sustaining HTC delivery. RESULTS: Only 39% (56/144) of planned SAIA visits were completed, largely due to the COVID-19 pandemic and a prolonged healthcare worker strike. In the final study quarter, 81.6% (160/196) of new clients at intervention facilities received HIV counseling, compared to 22.4% (55/245) in control facilities (prevalence rate ratio [PRR]=3.64, 95% confidence interval [CI]=2.68-4.94). HIV testing was conducted with 60.5% (118/195) of new family planning clients in intervention clinics, compared to 18.8% (45/240) in control clinics (PRR=3.23, 95% CI=2.29-4.55). Interviews with family planning clinic staff suggested institutionalization contributed to sustained HTC delivery, facilitated by low implementation strategy complexity and continued oversight. CONCLUSIONS: Intervention clinics demonstrated sustained improvement in HTC after SAIA was transitioned to DOHS leadership despite wide-scale healthcare disruptions and incomplete delivery of the implementation strategy. These findings suggest that system interventions may be sustained when integrated into DOHS programmatic activities. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02994355) registered on 16 December 2016.

Qualitative evaluation of the Systems Analysis and Improvement Approach as a strategy to increase HIV testing in family planning clinics using the Consolidated Framework for Implementation Research and the Implementation Outcomes Framework.

BACKGROUND: Significant gaps remain in HIV testing and counseling (HTC) in family planning (FP) clinics. To address these gaps, our group tested an implementation strategy called the Systems Analysis and Improvement Approach (SAIA), an evidenced-based multi-component implementation strategy focused on improving entire care cascades. In a cluster randomized trial of 24 FP clinics in Mombasa County, Kenya, SAIA led to a significant increase in HTC in intervention clinics compared to control clinics. The objective of this manuscript was to evaluate SAIA using the Consolidated Framework for Implementation Research (CFIR) and assess the Implementation Outcomes Framework outcomes of acceptability, appropriateness, and feasibility. METHODS: This qualitative assessment was nested within the cluster-randomized trial. Data collection included questionnaires to assess modifiable and non-modifiable health system factors related to HTC and in-depth interviews to query clinic norms, priorities, communication strategies, and readiness for change. The primary outcomes of interest were feasibility, appropriateness, and acceptability of SAIA. Data on inner setting and structural characteristics of FP clinics were collected to inform how context may impact outcomes. All interviews were recorded and analyzed using a rapid assessment approach. RESULTS: Of the 12 intervention clinics, 6 (50%) were public facilities. Availability of resources varied by clinic. Most clinics had a positive implementation climate, engaged leadership, and access to resources and information. While not all clinics identified HTC as a clinic priority, most reported a strong culture of embracing change and recognition of the importance of HIV testing within FP clinics. Interviews highlighted very high acceptability, appropriateness, and feasibility of SAIA. The implementation strategy was not complicated and fit well into existing clinic processes. In particular, staff appreciated that SAIA allowed clinic staff to generate contextually relevant solutions that they implemented. CONCLUSIONS: SAIA was implemented in FP clinics of varying sizes, capacity, and management support and was found to be acceptable, appropriate, and feasible. The agency that clinic staff felt in proposing and implementing their own solutions was likely part of SAIA's success. We anticipate this will continue to be a mechanism of SAIA's success when it is scaled up to more clinics in future trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02994355) registered 16 December 2016.