Systematic identification and characterization of genes in the regulation and biogenesis of photosynthetic machinery.

Photosynthesis is central to food production and the Earth's biogeochemistry, yet the molecular basis for its regulation remains poorly understood. Here, using high-throughput genetics in the model eukaryotic alga Chlamydomonas reinhardtii, we identify with high confidence (false discovery rate [FDR] < 0.11) 70 poorly characterized genes required for photosynthesis. We then enable the functional characterization of these genes by providing a resource of proteomes of mutant strains, each lacking one of these genes. The data allow assignment of 34 genes to the biogenesis or regulation of one or more specific photosynthetic complexes. Further analysis uncovers biogenesis/regulatory roles for at least seven proteins, including five photosystem I mRNA maturation factors, the chloroplast translation factor MTF1, and the master regulator PMR1, which regulates chloroplast genes via nuclear-expressed factors. Our work provides a rich resource identifying regulatory and functional genes and placing them into pathways, thereby opening the door to a system-level understanding of photosynthesis.

Evaluation of the therapeutic action of original antiviral drug in SARS-CoV-2.

Purpose of this article is to study the possible direct antiviral effect of "Armenikum" on SARS-CoV-2, conduct an in vitro study on the SARS-CoV-2 encephalomocarditis virus, and an in vivo study on the Syrian hamster model. Human coronavirus SARS-CoV-2 (delta strain) was used as the virus. Two groups of four-specimen hamsters were used to study the therapeutic activity of the drug during 48 h after infecting. One group of hamsters served as positive control and was infected with the virus at a similar dose as experimental one and was used as a control of pathology induced by the viral infection till the end of the experiment. Another group of hamsters (four of them) was injected physiological solution and was used as a control. The Syrian hamsters underwent a clinical blood test and computed tomography. "Armenikum" in the form of an injection has a significant antiviral effect on the human coronavirus SARS-CoV-2, credibly reducing the titers of the virus and the time of its elimination from the Syrian hamsters, significantly mitigating the viral infection. "Armenikum" in the form of an injection drug almost completely removes the pathological effect of the virus in the lungs of the hamsters.

Identifying racial disparities in the management of heart failure with reduced ejection fraction.

OBJECTIVE(S): Heart failure (HF) is chronic and progressive. Individuals with a left ventricular ejection fraction (LVEF or EF) < 40% are classified as having heart failure with reduced ejection fraction (HFrEF). Black patients have the highest incidence of HF and are more likely to suffer serious consequences from the disease. Identifying and addressing racial disparities in care is vital to ensuring health equity. The primary objective was to determine the association of race with 1-year heart HF admission rates for white and black patients, when adjusted for EF and age. The secondary objective was to determine the proportion of patients not on guideline-directed medication therapy (GDMT). DESIGN: This study was a retrospective chart review conducted between 10/22/2021 and 11/22/2022 of Veteran patients with HFrEF who were identified via the VA Heart Failure Dashboard. Only White and Black patients were included. A multivariable logistic regression was used to determine odds of admission due to HF. Pharmacotherapy was analyzed to identify gaps in GDMT and if racial disparities existed. SETTING AND PARTICIPANTS: Veterans within the Veterans Affairs Western New York Healthcare System. OUTCOME MEASURES: One-year HF admission rates for white and black patients, when adjusted for EF and age. Proportion of patients not on GDMT. RESULTS: Of the 345 patients with HF originally identified, 172 were included; 22% were admitted within one year. Black patients were 2.9 times more likely to be admitted. (P = 0.031). A median of two drugs (interquartile range [IQR] 1-3) could be added and one dose could be optimized (IQR 1-4) to reach GDMT goals. No differences were found in the prescribing of GDMT or in proportion of patients not on GDMT at recommended doses between white and black patients. CONCLUSION: Black patients were more likely to be admitted for HF than white patients. Pharmacists can play an important role in identifying the need for optimizing GDMT. Future studies could focus on pharmacist-led prospective interventions with an aim to close the gap in racial disparities.

Identifying racial disparities in the management of heart failure with reduced ejection fraction.

OBJECTIVE(S): Heart failure (HF) is chronic and progressive. Individuals with a left ventricular ejection fraction (LVEF or EF) < 40% are classified as having heart failure with reduced ejection fraction (HFrEF). Black patients have the highest incidence of HF and are more likely to suffer serious consequences from the disease. Identifying and addressing racial disparities in care is vital to ensuring health equity. The primary objective was to determine the association of race with 1-year heart HF admission rates for white and black patients, when adjusted for EF and age. The secondary objective was to determine the proportion of patients not on guideline-directed medication therapy (GDMT). DESIGN: This study was a retrospective chart review conducted between 10/22/2021 and 11/22/2022 of Veteran patients with HFrEF who were identified via the VA Heart Failure Dashboard. Only White and Black patients were included. A multivariable logistic regression was used to determine odds of admission due to HF. Pharmacotherapy was analyzed to identify gaps in GDMT and if racial disparities existed. SETTING AND PARTICIPANTS: Veterans within the Veterans Affairs Western New York Healthcare System. OUTCOME MEASURES: One-year HF admission rates for white and black patients, when adjusted for EF and age. Proportion of patients not on GDMT. RESULTS: Of the 345 patients with HF originally identified, 172 were included; 22% were admitted within one year. Black patients were 2.9 times more likely to be admitted. (P = 0.031). A median of two drugs (interquartile range [IQR] 1-3) could be added and one dose could be optimized (IQR 1-4) to reach GDMT goals. No differences were found in the prescribing of GDMT or in proportion of patients not on GDMT at recommended doses between white and black patients. CONCLUSION: Black patients were more likely to be admitted for HF than white patients. Pharmacists can play an important role in identifying the need for optimizing GDMT. Future studies could focus on pharmacist-led prospective interventions with an aim to close the gap in racial disparities.

Trends and overall survival after combined liver resection and thermal ablation of colorectal liver metastases: a nationwide population-based propensity score-matched study.

BACKGROUND: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS). METHODS: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2-3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes. RESULTS: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9-53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145). CONCLUSION: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases.

Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases: a population-based study.

INTRODUCTION: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM). METHODS: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan-Meier analysis on patients operated until 2018. RESULTS: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50-0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50-0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99-0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10-0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50-0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94-0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21. CONCLUSION: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery.

Ultrasound-Guided Peripheral Nerve Blocks for Shoulder Dislocation in the Emergency Department: A Systemic Review.

BACKGROUND: Shoulder dislocations are among the most common orthopedic emergencies encountered in the emergency department (ED). Ultrasound-guided peripheral nerve blocks (USG-PNBs) are increasingly being used for acute pain management in the ED, but clinical evidence supporting their utility for shoulder dislocation is limited and often conflicting. OBJECTIVE: The aim of this review was to summarize and evaluate the utility of USG-PNB for analgesia during closed reduction of dislocated shoulders in the ED. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search of the PubMed, Scopus, and Cochrane databases was performed from database inception to September 2022. We included clinical studies examining USG-PNB for pain management of dislocated shoulders in the ED. Information collected from eligible studies included patient demographic characteristics, USG-PNB approach, alternate analgesia techniques, anesthetic regimens, clinical outcomes, and adverse events. RESULTS: Five studies met inclusion criteria, all of which were randomized controlled trials comparing USG-PNB with procedural sedation and analgesia. Pooled patient satisfaction scores were similar for both analgesia methods (3.5 ± 0.6 vs. 3.9 ± 0.6 out of 5; p = 0.76). Patients managed with procedural sedation and analgesia achieved higher rates of overall shoulder reduction (100% vs. 67%; p < 0.001) and successful reduction on the first attempt (86% vs. 48%; p < 0.001). The USG-PNB groups in all but one study had shorter lengths of ED stay. Overall, USG-PNB was associated with a lower risk of adverse events and complications (3.9% vs. 24.9%; p < 0.001), especially adverse respiratory events (0% vs. 14.7%; p < 0.001). CONCLUSIONS: USG-PNBs performed by adequately trained emergency physicians should be considered a safe and effective alternative for analgesia during closed reduction of dislocated shoulders in the ED, particularly in patients with cardiorespiratory comorbidities.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

BACKGROUND: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. METHODS: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. RESULTS: Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). CONCLUSION: The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.

COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018­2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

Case-mix adjustment to compare colonoscopy performance between endoscopy centers: a nationwide registry study.

BACKGROUND : Nonmodifiable patient and endoscopy characteristics might influence colonoscopy performance. Differences in these so-called case-mix factors are likely to exist between endoscopy centers. This study aimed to examine the importance of case-mix adjustment when comparing performance between endoscopy centers. METHODS : Prospectively collected data recorded in the Dutch national colonoscopy registry between 2016 and 2019 were retrospectively analyzed. Cecal intubation rate (CIR) and adequate bowel preparation rate (ABPR) were analyzed. Additionally, polyp detection rate (PDR) was studied in screening colonoscopies following a positive fecal immunochemical test (FIT). Variation in case-mix factors between endoscopy centers and expected outcomes for each performance measure were calculated per endoscopy center based on case-mix factors (sex, age, American Society of Anesthesiologist [ASA] score, indication) using multivariable logistic regression. RESULTS: 363 840 colonoscopies were included from 51 endoscopy centers. Mean percentages per endoscopy center were significantly different for age > 65 years, male patients, ASA ≥ III, and diagnostic colonoscopies (all P < 0.001). In the FIT-positive screening population, significant differences were observed between endoscopy centers for age > 65 years, male patients, and ASA ≥ III (all P ≤ 0.001). The expected CIR, ABPR, and PDR ranged from 95.0 % to 96.9 %, from 93.6 % to 96.4 %, and from 76.2 % to 79.1 %, respectively. Age, sex, ASA classification, and indication were significant case-mix factors for CIR and ABPR. In the FIT-positive screening population, age, sex, and ASA classification were significant case-mix factors for PDR. CONCLUSION: Our findings emphasize the importance of considering case-mix adjustment when comparing colonoscopy performance measures between endoscopy centers.

Outcomes After Major Surgical Procedures in Octogenarians: A Nationwide Cohort Study.

INTRODUCTION: Aging of the worldwide population has been observed, and postoperative outcomes could be worse in elderly patients. This nationwide study assessed trends in number of surgical resections in octogenarians regarding various major surgical procedures and associated postoperative outcomes. METHODS: All patients who underwent surgery between 2014 and 2018 were included from Dutch nationwide quality registries regarding esophageal, stomach, pancreas, colorectal liver metastases, colorectal cancer, lung cancer and abdominal aortic aneurysms (AAA). For each quality registry, the number of patients who were 80 years or older (octogenarians) was calculated per year. Postoperative outcomes were length of stay (LOS), 30 day major morbidity and 30 day mortality between octogenarians and younger patients. RESULTS: No increase in absolute number and proportion of octogenarians that underwent surgery was observed. Median LOS was higher in octogenarians who underwent surgery for colorectal cancer, colorectal liver metastases, lung cancer, pancreatic disease and esophageal cancer. 30 day major morbidity was higher in octogenarians who underwent surgery for colon cancer, esophageal cancer and elective AAA-repair. 30 day mortality was higher in octogenarians who underwent surgery for colorectal cancer, lung cancer, stomach cancer, pancreatic disease, esophageal cancer and elective AAA-repair. Median LOS decreased between 2014 and 2018 in octogenarians who underwent surgery for stomach cancer and colorectal cancer. 30 day major morbidity decreased between 2014 and 2018 in octogenarians who underwent surgery for colon cancer. No trends were observed in octogenarians regarding 30 day mortality between 2014 and 2018. CONCLUSION: No increase over time in absolute number and proportion of octogenarians that underwent major surgery was observed in the Netherlands. Postoperative outcomes were worse in octogenarians.

The effect of display size on ultrasound interpretation.

OBJECTIVES: Ultrasound (US) is an essential component of emergency department patient care. US machines have become smaller and more affordable. Handheld ultrasound (HUS) machines are even more portable and easy to use at the patient's bedside. However, miniaturization may come with consequences. The ability to accurately interpret ultrasound on a smaller screen is unknown. This pilot study aims to assess how screen size affects the ability of emergency medicine clinicians to accurately interpret US videos. METHODS: This pilot study enrolled a prospective convenience sample of emergency medicine physicians. Participants completed a survey and were randomized to interpret US videos starting with either a phone-sized screen or a laptop-sized screen, switching to the other device at the halfway point. 50 unique US videos depicting right upper quadrant (RUQ) views of the Focused Assessment with Sonography in Trauma (FAST) examination were chosen for inclusion in the study. There were 25 US videos per device. All of the images were previously obtained on a cart-based machine (Mindray M9) and preselected by the study authors. Participants answered "Yes" or "No" in response to whether they identified free fluid. The time that each participant took to interpret each video was also recorded. Following the assessment, participants completed a post-interpretation survey. The goal of the pilot was to determine the accuracy of image interpretation on a small screen as compared to a laptop-sized screen. Statistical analyses were performed using MATLAB (The MathWorks, Inc., Natick, MA). Nonparametric statistical tests were utilized to compare subgroups, with a Wilcoxon signed rank test used for paired data and a Wilcoxon rank sum test for unpaired data. RESULTS: 52 emergency medicine physicians were enrolled in the study. The median accuracy of US interpretation for phone versus laptop image screen was 88.0% and 87.6% (p = 0.67). The mean time to interpret with phone versus laptop screen was 293 and 290 s (p = 0.66). CONCLUSIONS: The study found no statistically significant difference in the accuracy of US interpretation nor time spent interpreting when the pre-selected RUQ videos generated on a cart-based ultrasound machine were reviewed on a phone-sized versus a laptop-sized screen. This pilot study suggests that the accuracy of US interpretation may not be dependent upon the size of the screen utilized.

Hospital variation and outcomes of simultaneous resection of primary colorectal tumour and liver metastases: a population-based study.

BACKGROUND: The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of simultaneous resections and impact on hospital variation. METHOD: This population-based study included all patients who underwent liver surgery for synchronous colorectal liver metastases between 2014 and 2019 in the Netherlands. Factors associated with simultaneous resection were identified. Short-term surgical outcomes of simultaneous resections and factors associated with 30-day major morbidity were evaluated. RESULTS: Of 2146 patients included, 589 (27%) underwent simultaneous resection in 28 hospitals. Simultaneous resection was associated with age, sex, BMI, number, size and bilobar distribution of CRLM, and administration of preoperative chemotherapy. More minimally invasive and minor resections were performed in the simultaneous group. Hospital variation was present (range 2.4%-83.3%) with several hospitals performing simultaneous procedures more and less frequently than expected. Simultaneous resection resulted in 13% 30-day major morbidity, and 1% mortality. ASA classification ≥3 was independently associated with higher 30-day major morbidity after simultaneous resection (aOR 1.97, CI 1.10-3.42, p = 0.018). CONCLUSION: Distinctive patient and tumour characteristics influence the choice for simultaneous resection. Remarkable hospital variation is present in the Netherlands.

A Chemical Perspective of Pharmacology and Toxicology.

My chemical training provided a somewhat different perspective of biolo-gical problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.

Mobile messenger-initiated reminders improve longitudinal adherence in a community-based, opportunistic colorectal cancer screening program: A single-blind, crossover randomized controlled study.

BACKGROUND: The fecal immunochemical test (FIT) is a cost-effective colorectal cancer (CRC) screening tool. However, longitudinal adherence, a factor that is critical to the success to any FIT-based screening program, often is poor. The authors hypothesized that reminders sent via mobile messengers, such as WhatsApp, improve such adherence. METHODS: In the current single-blind, randomized study, subjects from an opportunistic FIT screening program who had a negative FIT result the year prior were randomly allocated (1:1) to receive either a 1-off reminder via the WhatsApp messenger (WR) 1 month prior to the due appointments or no reminder (NR). All subjects were blinded to study participation and group allocation. At 24 months after randomization, a crossover of intervention was performed among those individuals who remained in the FIT program. The primary outcome was FIT adherence, defined as the pick-up and on-time return of the FIT. The secondary outcome was FIT adherence after the crossover. RESULTS: A total of 500 subjects were randomized to receive WR (250 subjects) or NR (250 subjects). Three individuals were excluded from analysis (1 died and 2 underwent colonoscopy). Both the FIT pick-up rate (80.3% vs 59.3%; P < .001) and return rate (79.9% vs 57.3%; P < .001) were significantly higher in the WR group compared with the NR group. After crossover of intervention (452 subjects), the WR group again was found to have a higher FIT pick-up rate (79.1% vs 52.9%; P < .001) and return rate (78.2% vs 52.4%; P < .001). CONCLUSIONS: Text reminders sent via mobile messenger appear to improve the longitudinal adherence to FIT-based opportunistic CRC screening programs. The routine use of this technology in CRC screening should be considered.

Minimally Invasive Oncologic Upper Gastrointestinal Surgery can be Performed Safely on all Weekdays: A Nationwide Cohort Study.

BACKGROUND: Existing literature suggests deteriorating surgical outcome of esophagogastric surgery as the week progresses. However, these studies were conducted in the pre-centralization and pre-minimally invasive era. In addition, they failed to correct for fixed weekdays of esophagogastric cancer surgery among hospitals. This study aimed to describe the impact of weekday of minimally invasive upper gastrointestinal surgery on short-term surgical outcomes. METHODS: All patients registered in the Dutch Upper Gastrointestinal Cancer Audit who underwent curative minimally invasive esophageal or gastric carcinoma surgery in 2015-2019, were included in this nationwide cohort study. Using multilevel multivariable logistic regression, the impact of weekday of surgery on 14 short-term surgical outcomes was investigated. To correct for interhospital variance in fixed weekday(s) of surgery multilevel analyses was used. Results were adjusted for patient, tumor, and treatment characteristics using multivariable logistic regression analyses. RESULTS: This study included 4,102 patients undergoing minimally invasive upper gastrointestinal surgery (2,968 esophageal cancer and 1,134 gastric cancer patients). Weekday of surgery did not impact postoperative complications, severe postoperative complications, surgical/technical complications, medical complications, anastomotic leakage, complicated postoperative course, failure to rescue, surgical radicality, lymph node yield, 30-day/in-hospital mortality, reinterventions, length of ICU stay, 30-day readmission, and textbook outcome after neither esophageal cancer nor gastric cancer surgery. CONCLUSIONS: Minimally invasive esophagogastric surgery can be performed safely on all weekdays with respect to short-term surgical outcomes, which is important information for operation room scheduling.

CYP2D6 genotype may moderate measures of brain structure in methamphetamine users.

Chronic methamphetamine use is linked to abnormalities in brain structure, which may reflect neurotoxicity related to metabolism of the drug. As the cytochrome P450 2D6 (CYP2D6) enzyme is central to the metabolism of methamphetamine, genotypic variation in its activity may moderate effects of methamphetamine on brain structure and function. This study explored the relationship between CYP2D6 genotype and measures of brain structure and cognition in methamphetamine users. Based on the function of genetic variants, a CYP2D6 activity score was determined in 82 methamphetamine-dependent (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria) and 79 healthy-control participants who completed tests of cognitive function (i.e., attention, memory, and executive function); most were also evaluated with structural magnetic resonance imaging (MRI) (66 methamphetamine-dependent and 52 controls). The relationship between CYP2D6 activity score and whole brain cortical thickness differed by group (interaction p = 0.024), as increasing CYP2D6 activity was associated with thinner cortical thickness in the methamphetamine users (ß = -0.254; p = 0.035), but not in control subjects (ß = 0.095; p = 0.52). Interactions between CYP2D6 activity and group were nonsignificant for hippocampal volume (ps > 0.05), but both hippocampi showed trends similar to those observed for cortical thickness (negative relationships in methamphetamine users [ps < 0.05], and no relationships in controls [ps > 0.50]). Methamphetamine users had lower cognitive scores than control subjects (p = 0.007), but there was no interaction between CYP2D6 activity score and group on cognition (p > 0.05). Results suggest that CYP2D6 genotypes linked to higher enzymatic activity may confer risk for methamphetamine-induced deficits in brain structure. The behavioral consequences of these effects are unclear and warrant additional investigation.

Evaluation of health surveillance system attributes: the case of neglected tropical diseases in Kenya.

BACKGROUND: Control of preventive chemotherapy-targeted neglected tropical diseases (PC-NTDs) relies on strengthened health systems. Efficient health information systems provide an impetus to achieving the sustainable development goal aimed at ending PC-NTD epidemics. However, there is limited assessment of surveillance system functions linked to PC-NTDs and hinged on optimum performance of surveillance system attributes. The study aimed to evaluate surveillance system attributes based on healthcare workers' perceptions in relation to PC-NTDs endemic in Kenya. METHODS: A cross-sectional health facility survey was used to purposively sample respondents involved in disease surveillance activities. Consenting respondents completed a self-administered questionnaire that assessed their perceptions on surveillance system attributes on a five-point likert scale. Frequency distributions for each point in the likert scale were analysed to determine health workers' overall perceptions. Data was analysed using descriptive statistics and estimated median values with corresponding interquartile ranges used to summarise reporting rates. Factor analysis identified variables measuring specific latent attributes. Pearson's chi-square and Fisher's exact tests examined associations between categorical variables. Thematic analysis was performed for questionnaire open-ended responses. RESULTS: Most (88%) respondents worked in public health facilities with 71% stationed in second-tier facilities. Regarding PC-NTDs, respondents perceived the surveillance system to be simple (55%), acceptable (50%), stable (41%), flexible (41%), useful (51%) and to provide quality data (25%). Facility locality, facility type, respondents' education level and years of work experience were associated with perceived opinion on acceptability (p = 0.046; p = 0.049; p = 0.032 and p = 0.032) and stability (p = 0.030; p = 0.022; p = 0.015 and p = 0.024) respectively. Median monthly reporting timeliness and completeness rates for facilities were 75 (58.3, 83.3) and 83.3 (58.3, 100) respectively. Higher-level facilities met reporting timeliness (p < 0.001) and completeness (p < 0.001) thresholds compared to lower-level facilities. CONCLUSION: Health personnel had lower perceptions on the stability, flexibility and data quality of the surveillance system considering PC-NTDs. Reporting timeliness and completeness rates decreased in 2017 compared to previous surveillance periods. Strengthening all surveillance functions would influence health workers' perceptions and improve surveillance system overall performance with regard to PC-NTDs.

Assessment of surveillance core and support functions regarding neglected tropical diseases in Kenya.

BACKGROUND: Effective surveillance and response systems are vital to achievement of disease control and elimination goals. Kenya adopted the revised guidelines of the integrated disease surveillance and response system in 2012. Previous assessments of surveillance system core and support functions in Africa are limited to notifiable diseases with minimal attention given to neglected tropical diseases amenable to preventive chemotherapy (PC-NTDs). The study aimed to assess surveillance system core and support functions relating to PC-NTDs in Kenya. METHODS: A mixed method cross-sectional survey was adapted involving 192 health facility workers, 50 community-level health workers and 44 sub-national level health personnel. Data was collected using modified World Health Organization generic questionnaires, observation checklists and interview schedules. Descriptive summaries, tests of associations using Pearson's Chi-square or Fisher's exact tests and mixed effects regression models were used to analyse quantitative data. Qualitative data derived from interviews with study participants were coded and analysed thematically. RESULTS: Surveillance core and support functions in relation to PC-NTDs were assessed in comparison to an indicator performance target of 80%. Optimal performance reported on specimen handling (84%; 100%), reports submission (100%; 100%) and data analysis (84%; 80%) at the sub-county and county levels respectively. Facilities achieved the threshold on reports submission (84%), reporting deadlines (88%) and feedback (80%). However, low performance reported on case definitions availability (60%), case registers (19%), functional laboratories (52%) and data analysis (58%). Having well-equipped laboratories (3.07, 95% CI: 1.36, 6.94), PC-NTDs provision in reporting forms (3.20, 95% CI: 1.44, 7.10) and surveillance training (4.15, 95% CI: 2.30, 7.48) were associated with higher odds of functional surveillance systems. Challenges facing surveillance activities implementation revealed through qualitative data were in relation to surveillance guidelines and reporting tools, data analysis, feedback, supervisory activities, training and resource provision. CONCLUSION: There was evidence of low-performing surveillance functions regarding PC-NTDs especially at the peripheral surveillance levels. Case detection, registration and confirmation, reporting, data analysis and feedback performed sub-optimally at the facility and community levels. Additionally, support functions including standards and guidelines, supervision, training and resources were particularly weak at the sub-national level. Improved PC-NTDs surveillance performance sub-nationally requires strengthened capacities.

Feasibility of implementing recommendations to improve neglected tropical diseases surveillance and response in Kenya: a modified Delphi study.

BACKGROUND: Effective health information systems (HIS) are critical towards achieving timely response to preventive chemotherapy neglected tropical diseases (PC-NTDs) and their eventual elimination. Strengthened HIS enable prompt case detection and effective response to halt disease transmission and prevent probable outbreaks. This study aimed to assess the importance and feasibility of implementing recommendations for improving surveillance core functions, support functions and surveillance attributes concerning PC-NTDs in Kenya. METHODS: A descriptive web-based Delphi process comprising of two survey rounds was used to achieve group consensus on the importance of recommended actions and feasibility of their implementation. In the first round, participants were enrolled to complete a five-point likert-type self-administered electronic questionnaire comprising of 60 statements across 12 sub-domains on the importance of recommendations. In the second round, participants reappraised their responses following completion of a questionnaire with 56 rephrased statements on feasibility of implementing the recommendations to improve PC-NTDs surveillance and response. Data from both rounds were analysed using descriptive statistics and thematic analysis performed for the open-ended responses. RESULTS: Sixty-two key stakeholders actively involved in surveillance and response activities in seven PC-NTDs endemic counties in Kenya were invited to participate. Of these, 50/62 completed the first round (81 % response rate) and 45/50 completed the second round (90 % response rate). Consensus was achieved (defined as > 70 % agreement) on the importance (93 %) of recommendation statements and feasibility (82 %) of implementing the important recommendations. Stakeholders agreed on the importance and feasibility of specific recommendations across the 12 sub-domains: case detection and registration, reporting, data analysis, feedback, epidemic preparedness and response, supervision, training, resources, simplicity, acceptability, stability and flexibility. However, there was lack of consensus on the feasibility of conducting routine data analysis, increasing supervision of surveillance activities at lower levels and retaining trained surveillance staff across all levels. CONCLUSIONS: Consensus among health stakeholders on implementation of the important and feasible recommendations will inform relevant strategies for strengthening specific surveillance system functions in view of PC-NTDs in Kenya.

Short-term postoperative outcomes after liver resection in the elderly patient: a nationwide population-based study.

BACKGROUND: Liver resection is high-risk surgery in particular in elderly patients. The aim of this study was to explore postoperative outcomes after liver resection in elderly patients. METHODS: In this nationwide study, all patients who underwent liver resection for primary and secondary liver tumours in the Netherlands between 2014 and 2019 were included. Age groups were composed as younger than 70 (70-), between 70 and 80 (septuagenarians), and 80 years or older (octogenarians). Proportion of liver resections per age group and 30-day major morbidity and 30-day mortality were assessed. RESULTS: In total, 6587 patients were included of whom 4023 (58.9%) were younger than 70, 2135 (32.4%) were septuagenarians and 429 (6.5%) were octogenarians. The proportion of septuagenarians increased during the study period (aOR:1.06, CI:1.02-1.09, p < 0.001). Thirty-day major morbidity was higher in septuagenarians (11%) and octogenarians (12%) compared to younger patients (9%, p = 0.049). Thirty-day mortality was higher in septuagenarians (4%) and octogenarians (4%) compared to younger patients (2%, p < 0.001). Cardiopulmonary complications occurred more frequently with higher age, liver-specific complications did not. Higher age was associated with higher 30-day morbidity and 30-day mortality in multivariable logistic regression. CONCLUSION: Thirty-day major morbidity and 30-day mortality are higher after liver resection in elderly patients, attributed mainly to non-surgical cardiopulmonary complications.