Non-significant Decline Research Articles

Drug and Neurofilament Levels in Serum and Breastmilk of Women With Multiple Sclerosis Exposed to Natalizumab During Pregnancy and Lactation.

ObjectiveTo determine the transfer of the monoclonal antibody natalizumab into breastmilk and to evaluate drug and serum neurofilament light chain ((s)NfL) levels in natalizumab exposed pregnancies and lactation periods.MethodsEleven women with relapsing remitting multiple sclerosis treated with natalizumab during pregnancy and lactation were included in this study. Breastmilk samples were collected up to 302 days after delivery and analyzed for natalizumab concentration and NfL. Additionally, maternal drug levels and sNfL were determined preconceptually, in each trimester, at delivery and postpartum. Clinical and radiological disease activity was systemically assessed across pregnancy and postpartum period.ResultsThe mean average natalizumab concentration in breast milk was low at 0.06 µg/ml [standard deviation (SD) 0.05] in the eight patients who provided serial breastmilk samples with an estimated mean absolute infant dose of 0.007 mg/kg/d (SD 0.005). The relative infant dose (RID), a metric comparing the infant with maternal drug exposure was low as well with a mean of 0.04% (SD=0.03). Most patients had a maximum concentration in breast milk at one to eight days after infusion. Pregnancy was associated with a non-significant decline of the median natalizumab serum concentration. All patients exposed to natalizumab prior (n=10) and during pregnancy (n=11) kept free of disease activity during gestation. While pregnancy was associated with low sNfL levels in patients treated with natalizumab prior and during pregnancy, the postpartum period was linked to a transient sNfL increase in some patients without any evidence of clinical or radiological disease activity. NfL was detectable in the majority of breastmilk samples with a median concentration of 1.7 pg/ml (range 0.004-18.1).ConclusionWe determined transfer of natalizumab into breastmilk with an RID far below the threshold of concern of 10%. Studies including childhood development assessment are needed in order to gain safety data about natalizumab-exposed breastfeeding. SNfL assessment might be a useful adjunct to monitor silent disease activity and therapeutic response during pregnancy and postpartum period. However, further investigations regarding transient postpartum sNfL increases are required to determine its association to parturition per se or to a silent disease activity in people with multiple sclerosis.

Bird-window collisions: Mitigation efficacy and risk factors across two years.

BackgroundResearch on bird-window collision mitigation is needed to prevent up to a billion bird fatalities yearly in the U.S. At the University of Utah campus (Salt Lake City, Utah, USA), past research documented collisions, especially for Cedar Waxwings (Bombycilla cedrorum) drawn to fruiting ornamental pears in winter. Mirrored windows, which have a metallic coating that turns window exteriors into mirrors, had frequent collisions, which were mitigated when Feather Friendly®bird deterrent markers were applied. Bird-friendly windows–ORNILUX®ultraviolet (UV) and fritted windows–also reduced collisions when data were collected across fall and winter. Extending this prior research, we evaluated additional mitigation and tested the replicability of effects for pear trees, mirrored windows, and bird-friendly windows across two years.MethodsUsing published data from eight buildings monitored for collisions in year 1 (Fall and Winter, 2019–2020), we added another year of monitoring, Fall and Winter, 2020–2021. Between years, Feather Friendly®mitigation markers were added to collision-prone areas of two buildings, including both mirrored and transparent windows.ResultsThe two buildings that received new Feather Friendly®mitigation had significantly fewer collisions post-mitigation. Control areas also had nonsignificant decline in collisions. The interaction of area (mitigation vs. control) by time (year 1 vs. 2) was significant, based on generalized estimating equations (GEE). The total yearly collisions across all eight buildings declined from 39 to 23. A second GEE analysis of all 8 buildings showed that mirrored windows, pear trees, and bird-friendly windows were each significant when analyzed separately. The best-fit model showed more collisions for mirrored windows and fewer collisions for bird-friendly windows. We found pear tree proximity to be related to more collisions in winter than fall. In addition, pear trees showed reduced collisions from year 1 to 2, consistent with new mitigation for two of three buildings near pear trees.DiscussionFeather Friendly® markers can mitigate collisions with transparent windows, not only mirrored windows, compared to unmitigated areas over 2 years. Results also underscore the dangers of pear tree proximity and mirrored windows and the efficacy of bird-friendly windows. Thus, bird collisions can be prevented by window mitigation, permanent bird-friendly windows, and landscape designs that avoid creating ecological traps.

Associations between smoke-free vehicle legislation and childhood admissions to hospital for asthma in Scotland: an interrupted time-series analysis of whole-population data

In Scotland, childhood admissions to hospital for asthma fell from March, 2006, after legislation was introduced to prohibit smoking in public places. In December, 2016, new Scottish legislation banned smoking in vehicles containing a child. We aimed to determine whether the introduction of this new legislation produced additional benefits. We obtained data on all asthma emergency admissions to hospitals in Scotland between 2000 and 2018 for individuals younger than 16 years. We used interrupted time-series analyses to study changes in monthly incidence of asthma emergency admissions to hospital per 100 000 children after the introduction of smoke-free vehicle legislation, taking into account previous smoke-free interventions. We did subgroup analyses according to age and area deprivation, using the Scottish Index of Multiple Deprivation, and repeated the analyses for a control condition, gastroenteritis, and other respiratory conditions. Of the 32 342 emergency admissions to hospital for asthma among children younger than 16 years over the 19-year study period (Jan 1, 2000, to Dec 31, 2018), 13 954 (43%) were among children younger than 5 years and 18 388 (57%) were among children aged 5-15 years. After the introduction of smoke-free vehicle legislation, there was a non-significant decline in the slope for monthly emergency admissions to hospital for asthma among children younger than 16 years (-1·21%, 95% CI -2·64 to 0·23) relative to the underlying trend in hospital admissions for childhood asthma. However, children younger than 5 years had a significant decline in the slope for monthly asthma admissions (-1·49%, -2·69 to -0·27) over and above the underlying trend among children in this age group (equivalent to six fewer hospitalisations per year), but no such decline was seen in children aged 5-15 years. Monthly admissions to hospital for asthma fell significantly among children living in the most affluent areas (-2·27%, -4·41 to -0·07) but not among those living in the most deprived areas. We found no change in admissions to hospital for gastroenteritis or other respiratory conditions after the introduction of the smoke-free vehicle legislation. Although legislation banning smoking in vehicles did not affect hospital admissions for severe asthma among children overall or in the older age group, this legislation was associated with a reduction in severe asthma exacerbations requiring hospital admission among preschool children, over and above the underlying trend and previous interventions designed to reduce exposure to second-hand smoke. Similar legislation prohibiting smoking in vehicles that contain children should be adopted in other countries. None.

Spectrum of Disease Severity in Nonsyndromic Patients With Mutations in the CEP290 Gene: A Multicentric Longitudinal Study.

PurposeThe purpose of this study was to perform a detailed longitudinal phenotyping and genetic characterization of 32 Italian patients with a nonsyndromic retinal dystrophy and mutations in the CEP290 gene.MethodsWe reviewed the clinical history and examinations of 32 patients with a nonsyndromic retinal dystrophy due to mutations in the CEP290 gene, followed up (mean follow-up: 5.9 years) at 3 Italian centers. The clinical examinations included: best corrected visual acuity (BCVA), optical coherence tomography (OCT), and full-field electroretinogram (ERG).ResultsPatients (mean age = 19.0 ± 3.4 years) had a mean BCVA of 1.73 ± 0.20 logMAR. Longitudinal analysis of BCVA showed a nonsignificant decline. Central retinal thickness (CRT) declined significantly with age at an exponential rate of 1.0%/year (P = 0.001). At disease onset, most patients (19/32; 49.4%) had nystagmus. The absence of nystagmus was significantly associated with better BCVA and more preserved CRT (P < 0.05). ERG showed undetectable responses in most patients (64.0%), whereas reduced scotopic and photopic responses were observed in four patients (16.0%) who had no nystagmus. We identified 35 different variants, among which 12 were novel. Our genotype-phenotype correlation analysis shows a significantly worse BCVA in patients harboring a loss-of-function mutation and the deep-intronic variant c.2991+1655A>G.ConclusionsOur study highlights a mild phenotype of the disease, characterized by absence of nystagmus, good visual acuity, considerably preserved retinal morphology, and recordable ERG, confirming the wide spectrum of CEP290-related retinal dystrophies. Finally, in our cohort, the deep intronic variant c.2991+1655A>G was associated with a more severe phenotype.

The effect of Astaxanthin on Experimentally Induced Diabetic Kidney Disease

Aim: To identify the potential renal protective effect produced by astaxanthin on streptozotocin-produced diabetic kidney disease in rats.&#x0D; Study Design: Male Wistar rats (n=60) were separated into six groups, control, diabetic (streptozotocin 45 mg/kg single intraperitoneal injection), diabetic + ramipril (1 mg/kg oral gavage), diabetic + astaxanthin (10mg/kg oral gavage), diabetic + astaxanthin (50 mg/kg oral gavage), and astaxanthin-alone (50 mg/kg oral gavage) group.&#x0D; Place and Duration of Treatment: Department of Pharmacology, College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. Duration of treatment was eight weeks.&#x0D; Methodology: Fasting blood glucose, and symptoms of diabetes were evaluated weekly. Kidneys were evaluated by measuring serum creatinine level, kidney index, and hematoxylin and eosin staining.&#x0D; Results: Eight-week astaxanthin treatment (50 mg/kg) in streptozotocin-produced diabetic kidney disease in rats significantly alleviated the diabetic symptoms (p = 0.05), and the decrease in body weight (P = .05) compared to nontreated diabetic rats. Nonetheless, the same dose produced a nonsignificant decline in fasting blood glucose level contrasted to diabetic rats (P = .45). Kidney index and serum creatinine of diabetic rats were significantly attenuated by both 10 and 50 mg/kg astaxanthin doses (P = .05). Additionally, renal architecture was preserved by high-dose astaxanthin treatment compared to nontreated diabetic rats.&#x0D; Conclusion: Astaxanthin could protect against kidney damage associated with diabetes. Nevertheless, the impact of astaxanthin on biological markers of kidney damage in diabetes and the molecular pathways implicated in diabetic kidney disease requires additional investigation.

Risk areas for Human Visceral Leishmaniosis 2007-2018: A temporal and spatial analysis in Ceará, Brazil.

Visceral leishmaniasis (VL) is considered as an important tropical disease because it rapidly spreads across a wide geographical area. This study aimed to analyse the temporal and spatial patterns of incidence, mortality and case fatality rates due to human VL in Ceará, Brazil, from 2007 to 2018. This is an ecological study involving time series and spatial analyses, and data were obtained from human VL notifications. Temporal trend analysis was carried out using the Joinpoint Regression Program. SaTScan 9.6 was used for conducting spatial analyses, and ArcMap 9.2 was used for building maps. There were 6,066 incident cases and 516 deaths due to human VL. There was an increasing trend in the incidence rate from 2007 to 2014 (annual per cent change [APC]=3.8; 95% confidence interval [CI]:0.5 to 7.3; p=.031). Mortality (APC=-0.3; 95%CI: -2.5 to 1.9; p=.765) and VL case fatality rates (APC=-3.0; 95%CI: -4.3 to -1,7; p=.188) showed non-significant decline. The incidence rates were higher in the northwest and south regions of the state, with 11 high incidence rate clusters from 2007 to 2010, seven clusters in 44 municipalities from 2011 to 2014, and six clusters in 49 municipalities from 2015 to 2018. During 2007-2010, only one significant mortality rate cluster was identified in the southern region (relative risk [RR]=7.6); during 2011-2014, two clusters in the northwest region were identified (RR=3.9 and RR=4.6). In the last period, a cluster of 11 municipalities in the southern region was identified (RR=4.2). Mortality rate clusters were identified in the centre-south (2007-2010), northwest and south (both from 2011 to 2018). VL has a heterogeneous distribution, with maintenance of clusters with high incidence and mortality rates, as well as case fatality rates in municipalities in the northwest and south regions. These clusters present areas with the greatest risk of transmission of human VL.

Comparative Analysis of Cocoyam Varieties on Yield under Irrigation in Kano State, Nigeria

This study was carried out to compare the growth rate and yield of Xanthosomasagittaifolium and Colocasiaesculenta cultivated under irrigation with NPK 15:15:15 fertilizer application at the rates of (100kg) and cow dung at the rate of 20t/ha respectively at two different locations. This was aimed at identifying growth rate and tuber yield potentials of the cocoyam cultivars on different experimental condition. The two locations used for the study were the Agricultural Education Research Farm; Federal College of Education (Tech) Bichi and Watari Irrigation Scheme site along Bichi-Bagwai and Gwarzo road. The two cultivars cultivated were replicated at both sites. The result showed that application of NPK 15:15:15 fertilizer increased growth rate (height and leaf size) of Xanthosomasagittaifolium with a mean value of 39.66 and 31.94, while the tuber yield has a mean value of 2.23 at WatariIrrigation Scheme respectively. Also, Colocasiaesculenta cultivated at Agricultural Education Research Farm with organic manure application has a higher tuber yield mean value of 1.98 than those at WatariIrrigation Scheme. The highest tuber yield of Xanthosomasagittaifolium was realized in response to the application of 100kg/ha NPK fertilizer application. Further increases above these rates in the locations caused non-significant decline in tuber yield. However, Colocasiaesculentacultivated at Imane(Major Producing Area) with organic manure application yielded better than those cultivated at WatariIrrigation Scheme with organic manure application under irrigation. The study concluded that both Xanthosomasagittaifolium and Colocasiaesculentacan be cultivated under irrigation. It was recommended that these cocoyam cultivars should be made available to farmers for trial and subsequent adoption through collaboration with extension agents. This will on the long run contribute to enhance and promote food security in Kano State and Nigeria at large.

Memory outcomes of temporal lobe surgery in adults aged over 45years.

It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45years of age compared with younger patients. We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome. The presurgical MQ (median 88) in ≥45years age group was significantly lower than in both younger groups (median MQ=100 for ≤30years age group, p=0.002; median MQ=107 for 31-44years age group, p=0.002). Three years after the surgery, the MQ decreased significantly in ≤30years age group (p=0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome. Higher age at the time of surgery does not significantly increase the risk for postsurgical memory decline; however, older patients are more likely to have lowered presurgical MQ. We did not find significant differences in the impact of surgery on seizure outcome among the age groups. Epilepsy surgery appears to be a safe and effective method in the age over 45years even though an earlier surgery should be preferred.

Effects of implementing a postabortion care strategy in Kinshasa referral hospitals, Democratic Republic of the Congo

ObjectivesTo evaluate the effects of the implementation of a postabortion care (PAC) strategy in Kinshasa referral hospitals, this study analyzed the quality of postabortion care services, including postabortion contraception, and the duration of hospitalization.MethodologyWe estimated the effects of the PAC strategy using a quasi-experimental study by evaluating the outcomes of 334 patients with the diagnosis of a complication of induced abortion admitted to 10 hospitals in which the PAC strategy was implemented compared to the same outcomes in 314 patients with the same diagnosis admitted to 10 control facilities from 01/01/2016 to 12/31/2018. In response to government policy, the PAC strategy included the treatment of abortion complications with recommended uterine evacuation technology, the family planning counseling and service provision, linkages with other reproductive health services, including STI evaluation and HIV counseling and/or referral for testing, and partnerships between providers and communities. The information was collected using a questionnaire and stored using open data kit software. We supplemented this information with data abstracted from patient records, facility registries of gynecological obstetrical emergencies, and family planning registries. We analyzed data and developed regression models using STATA15. Thus, we compared changes in use of specific treatments and duration of hospitalization using a "difference-in-differences" analysis.ResultsThe implementation of PAC strategy in Kinshasa referral hospitals has resulted in the utilization of WHO recommended uterine evacuation method MVA (29.3% more in the experimental structures, p = 0.025), a non-significant decline in sharp-curettage (19.3% less, p = 0.132), and a decline in the duration of hospitalization of patients admitted for PAC (1 day less, p = 0.020). We did not observe any change in the use of PAC services, mortality, and the provision of post abortion contraception.ConclusionDespite significant improvement in the management of PAC, the uptake in WHO approved technology—namely MVA, and the duration of hospitalization, these outcomes while a significant improvement for DRC, indicate that additional quality improvement strategies for management of PAC and risk-mitigating strategies to reduce barriers to care are required.

Well-being and COVID-19-related worries of German children and adolescents: A longitudinal study from pre-COVID to the end of lockdown in Spring 2020.

BackgroundThere is concern that pandemic measures put a strain on the health and well‐being of children. We investigated the effects of the COVID‐19 pandemic, the lockdown, and social distancing on the well‐being, media use, and emotions of children and adolescents between 9 and 18 years.MethodsWe used linear and proportional odds logistic regression correcting for age, sex, and socioeconomic status (SES) and to compare media use, peers/social support, physical, and psychological well‐being between 2019 (pre‐COVID baseline) and two time points shortly after the start of the lockdown (last week of March and April 2020, respectively) in 391 9–19‐year‐old healthy children and adolescents of the LIFE Child cohort. COVID‐19‐related feelings and their relationship to age, sex, and SES were assessed at two time points during lockdown.ResultsWe found significantly lower scores in physical and psychological well‐being during lockdown compared to baseline. The effect was significantly stronger in children with medium/low SES. Perceived social support scores were also significantly lower during the lockdown. The percentage of children who had no contact with their peers (in‐person or online) increased from 3% pre‐COVID to 14% and 13% in April and March 2020, respectively. About 80% of the children missed in‐person contacts with friends. Most of the children worried more about the health of their families than their own. Sixty percent worried about the international situation at least moderately, whereas only 20% were afraid of COVID‐19 itself. The percentage of children who believed it would never be as before COVID‐19 rose from 7.4% at the beginning lockdown end of March to 16.2% a month later. In contrast, all other COVID‐19‐related worries, showed a (nonsignificant) decline during the same period.ConclusionOur study supports the notion that pandemic measures have to be balanced against adverse public health effects. Especially vulnerable groups have to be protected.

Temporal Trend of Conventional Sperm Parameters in a Sicilian Population in the Decade 2011-2020.

Objective: To evaluate the changes of conventional sperm parameters in men who referred to an andrology reference center in Catania (Eastern Sicily, Italy) in the decade 2011–2020. Methods: For this purpose, we selected–retrospectively and randomly–the reports of 1409 semen analyses performed according to the 2010 WHO criteria. Data on sperm concentration, total sperm count, progressive sperm motility, and percentage of normal forms were analyzed using linear regression of the raw and logarithmic-transformed data. The sperm parameters were subsequently pooled in two five-year periods (2011–2015 and 2016–2020) and compared with each other. Finally, the influence of the city of residence was assessed on five-year pooled data. Main results: A slight but non-significant decline of total sperm count (−2.26 million/year; p = 0.065) and the percentage of spermatozoa with normal morphology (−0.08%/year; p = 0.057) was observed. In contrast, a significant increase of progressive sperm motility (+0.28%/year; p = 0.008) over time was found. The total sperm count of the quinquennium 2016–2020 was significantly lower. and an upward trend of progressive sperm motility was found. compared to the years 2011–2015. No changes in sperm concentration and morphology occurred in the years 2011–2015 vs. 2016–2020. Sperm conventional parameters did not differ when the five-year pooled data were analyzed according to the town of residence. Conclusions: Divergent trends of total sperm count and progressive sperm motility over time were found in patients from Eastern Sicily. This may point out the need of assessing whether a time-dependent change of biofunctional sperm parameters occurs to really understand the trend of sperm quality over time.

An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5years post-surgery.

To investigate the mid-term outcomes of an accelerated return to full weight bearing (WB) after matrix-induced autologous chondrocyte implantation (MACI). This randomized study allocated 35 patients (37 knees) to a 6 week (n = 18) or 8 week (n = 19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2 and minimum 5years (range 5.5-7years), using the KOOS, SF-36, visual analogue pain scale, 6-min walk test and active knee range of motion (ROM). Peak isokinetic knee extensor and flexor strength was assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) was undertaken to evaluate the repair tissue, and an MRI composite score was calculated. While no group differences (n.s.) were observed, significant improvement was observed for all patient-reported outcome measures (p < 0.05), 6-min walk distance (p = 0.040), active knee flexion (p = 0.002) and extension (p < 0.0001) ROM, and the LSI for peak knee extensor strength (p < 0.0001). At final review, 87.5% (6weeks) and 82.4% (8weeks) of patients were satisfied overall. A non-significant decline (n.s.) was observed for the MRI composite score from 1-year post-surgery to final review, with no significant MRI-based differences (n.s.) between groups. At final review, two grafts (6-week n = 1, 8-week n = 1) demonstrated MRI-based graft failure, while an additional patient had progressed toward knee arthroplasty (8.1% failure rate at minimum 5years). The 6-week return to full WB after MACI provided comparable clinical and MRI-based outcomes beyond 5years post-surgery, without jeopardizing the graft. This 6-week WB protocol is faster than those previously proposed and studied. II.

Sonographic Optic Nerve Sheath Diameter Following Seizure Prophylaxis in Pre-Eclamptic Parturients With Severe Features: A Prospective, Observational Study.

Neurological manifestations, including raised intracranial pressures, are a hallmark of worsening pre-eclampsia. Invasive methods for measuring intracranial pressure, though a gold standard, are not always a viable option. Maternal ocular sonography is a promising bedside tool, which serves as a noninvasive, cost-effective means for measuring optic nerve sheath diameter (ONSD), a surrogate marker of raised intracranial pressures. We studied the ultrasonographically measured ONSD in severely pre-eclamptic women, and the effect of magnesium sulfate therapy on its values. Thirty severely pre-eclamptic women at ≥28 weeks gestation were included. We recorded baseline ONSD values, serum magnesium levels, neurological symptoms, vitals, and repeated them at 4 and 12 hours following magnesium sulfate therapy, and then at 24 hours postpartum. An ONSD value >5.8 mm was suggestive of raised intracranial pressure. Primary outcome measure was to evaluate changes in ultrasonographically measured ONSD following seizure prophylaxis with magnesium sulfate. Women, 73.3%, had baseline ONSD >5.8 mm, with mean diameter being significantly high (6.02 ± 0.77 mm). There was a statistically nonsignificant decline in mean ONSD values at 4 and 12 hours, as well as at 24 hours postpartum. Patients with neurological symptoms declined significantly (from 70 to 10%; p value <.001) following magnesium sulfate therapy. Majority of severely pre-eclamptic parturients had high ONSD value suggestive of raised intracranial pressures, which persisted in the postpartum period and was unaffected by magnesium sulfate therapy. Ultrasound can thus serve as a point-of-care, cost-effective, easily available bedside tool for indirectly measuring intracranial pressures in this high-risk population.

Long-term Prospective Clinical and Magnetic Resonance Imaging–Based Evaluation of Matrix-Induced Autologous Chondrocyte Implantation

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging midterm clinical outcomes, although published studies presenting longer-term clinical and radiological outcomes, across varied tibiofemoral and patellofemoral graft locations, are scarce. Purpose: To present the clinical and radiological outcomes a minimum of 10 years after surgery in a consecutive series of patients who underwent MACI in the tibiofemoral or patellofemoral knee joint. Secondly, to investigate any association between outcomes and patient characteristics, graft parameters, and injury and surgery history. Study Design: Case series; Level of evidence, 4. Methods: Overall, 87 patients (99 grafts: 57 medial femoral condyle, 24 lateral femoral condyle, 11 trochlea, 7 patella) were prospectively evaluated clinically and with magnetic resonance imaging (MRI) before surgery and at 2, 5, and minimum 10 years after MACI (mean, 13.1 years; range, 10.5-16 years). Patients were evaluated with a range of patient-reported outcome measures (PROMs), including the Knee injury and Osteoarthritis Outcome Score (KOOS) and patient satisfaction. The 6-minute walk test, active knee range of motion, and peak isokinetic knee extensor and flexor strength were assessed. Limb symmetry indices (LSIs) were calculated for strength measures. MRI was undertaken to evaluate the repair tissue, and an MRI composite score was calculated. Results: All PROMs significantly improved (P < .05) over the pre- to postoperative period. Apart from KOOS Sport (P = .018) and the LSI for peak isokinetic knee extensor strength (P = .005), which significantly improved, no significant change (P > .05) was observed from 2 years after surgery to final follow-up (range, 10.5-16 years) in all other PROMs, 6-minute walk distance, active knee range of motion, and the LSI for peak isokinetic knee flexor strength. At final follow-up, while the mean LSIs for peak isokinetic knee flexor and extensor strength were 96.9% and 95.7%, respectively, 74.7% of patients were satisfied with their ability to participate in sports, and 88.5% were satisfied overall. A nonsignificant decline was observed for tissue infill (P = .211) and the MRI composite score (P = .099) from 2 years to final review. At final MRI review, 9 grafts (9.1%) had failed. While no significant association (P > .05) was observed between clinical or MRI-based outcomes and patient demographics (age, body weight, body mass index), defect size, or the duration of preoperative symptoms, the number of previous surgical procedures was significantly and negatively associated with KOOS Symptoms (P = .015), KOOS Sport (P = .011), and the degree of tissue infill (P = .045). Conclusion: MACI provided high levels of satisfaction and adequate graft survivorship as visualized on MRI at 10.5 to 16 years after surgery.

Vascular injury-related in-hospital mortality in Ontario between 1991 and 2009.

ObjectiveTrauma-related vascular injuries are major contributors to morbidity and mortality worldwide. We conducted a retrospective, population-based, cross-sectional study to examine temporal trends and factors associated with traumatic vascular injury-related in-hospital mortality in Ontario, Canada from 1991 to 2009.MethodsWe obtained data on Ontario hospital admissions for traumatic vascular injury, including injury mechanism and body region; and patient age, sex, socioeconomic status, and residence from the Canadian Institute for Health Information Discharge Database and Registered Persons Database from fiscal years 1991 to 2009. We performed time series analysis of vascular injury-related in-hospital mortality rates and multivariable logistic regression analysis to identify significant mortality-associated factors.ResultsThe overall in-hospital mortality rate for trauma-related vascular injury was 5.5%. A slight but non-significant decline in mortality occurred over time. The likelihood of vascular injury-related in-hospital mortality was significantly higher for patients involved in transport-related accidents (odds ratio [OR[=2.21, 95% confidence interval [CI], 1.76–2.76), age ≥65 years (OR = 4.34, 95% CI, 2.25–8.38), or with thoracic (OR = 2.24, 95% CI, 1.56–3.20) or abdominal (OR = 2.45, 95% CI, 1.75–3.42) injuries.ConclusionsIn-hospital mortality from traumatic vascular injury in Ontario was low and stable from 1991 to 2009.

Association Between Statewide Financial Incentive Programs and COVID-19 Vaccination Rates

To encourage COVID-19 vaccination, many states in the US have introduced financial incentives ranging from small, guaranteed rewards to lotteries that give vaccinated individuals a chance to win $1 million or more. We compiled information on statewide incentive programs along with data on daily vaccine doses administered per 100,000 individuals in each state. Leveraging variation across states in the daily presence of incentives, we used difference-in-differences regressions to examine the association between these incentive program indicators and vaccination rates. Difference-in-differences analysis showed that 24 statewide incentive programs were associated with a non-significant relative decline in daily vaccination rates of 8.9 per 100,000 individuals (95% CI [-64.3,46.5]; p=0.75). Furthermore, there was no significant difference in vaccination trends between states with and without incentives in any of the 14 days before or after incentives were introduced. Lotteries and other incentives offered by 24 states were not associated with a significant change in COVID-19 vaccination rates. More substantial incentives or mandates may be necessary to raise vaccination rates.

Effects of empagliflozin on proinflammatory cytokines and other coronary risk factors in patients with type 2 diabetes mellitus: A single-arm real-world observation.

This single-arm real-world observation aims to examine the effects of empagliflozin (EMPA) on coronary risk factors among subjects with known diabetes. Records of 63 subjects with type 2 diabetes mellitus, receiving EMPA were drawn for this study. Of 63 patients with diabetes, 6 were excluded, and the remaining 57 received EMPA (25mg/day) for 24weeks. Clinical data, dietary intakes, and physical activity were assessed by validated questionnaires. Treatment with EMPA was associated with significant decline in fasting and 2-hour post-prandial blood glucose and Hb1c indicating that this agent has potential antidiabetic effects. Pro-inflammatory cytokines; C-reactive protein, TNF-α, and interleukin-6 showed significant reduction after treatment with EMPA, compared to baseline levels. Apart from these changes, parameters of oxidative stress, thiobarbituric acid reactive substances, malondialdehyde, and diene conjugates as well as uric acid, showed a significant decline with an increase in antioxidant vitamins A, E, and C and beta-carotene as well as nitrite. There was a significant decline in serum uric acid, systolic and diastolic blood pressures, and angiotensin-converting enzyme (ACE), with a non-significant reduction in body weight and body mass index as well as in waist circumference of modest significance, after intervention of 12weeks compared to baseline levels. Total cholesterol, VLDL cholesterol and triglycerides showed non-significant decline compared to baseline levels. It is possible that EMPA administration can cause a significant decline in pro-inflammatory cytokines along with blood glucose, Hb1c, oxidative stress, uric acid, blood pressures, and ACE with an increase in antioxidant vitamins and nitrite. Randomized, controlled intervention trials would be necessary to confirm our findings.

Zinc supplementation in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study. (ZisCKDu-P)

Introduction: It was hypothesized that the antioxidant properties of zinc retard the progression of chronic kidney disease of unknown etiology in the North Central Province of Sri Lanka. Methods: The pilot study was a randomized, placebo-controlled, single blinded, parallel group, single-center clinical trial with two arms (Z and P) and a 1:1 allocation ratio. Participants in group Z (n=20) received 60 mg of elemental zinc daily, in the form of zinc sulfate, and group P (n=21) received a starch tablet per day. Clinical, hematological parameters and kidney function were measured at the baseline and following three months of the intervention. Results: A total of 86 CKDu patients were screened; only 35 males and 6 females were selected. Mean age and estimated glomerular filtration rate of the study population were 51.2±6.2 years and 38.9±8.8 mL/min/1.73 m2 respectively. At the end of three months there was non-significant increase in urine protein creatinine ratio (Z arm: 65±54 vs. 82± 86 mg/mmol; P=0.46, P arm: 72.4±113 vs. 120± 209 mg/mmol; P=0.36) and non-significant decline in estimated glomerular filtration rate (Z arm: 40.9±10.4 vs. 39.7±9.2 mL/min/1.73 m2; P=0.31, P arm: 37.1±6.8 vs. 36.4±10 mL/min/1.73m2; P=0.31) in both groups. Body mass index was significantly reduced (23±4 vs. 22.7± 3.9 kg/m2; P=0.01) and diastolic blood pressure was significantly increased (78±6 vs. 86±10 mmHg; P=0.001) in the placebo arm. Haemoglobin levelshowed a decline in the study group; 0.33±1 g/dl, while there was an increase in the placebo group, 0.34±0.7 g/dl, (P=0.02). There were no major side effects. Conclusions: The change of urine protein: creatinine ratio and estimated glomerular filtration rate did not show a significant difference between the two groups. A future trial should test effectiveness of same dose of zinc for a similar duration of time in a larger sample. Extended follow-up of the study subjects for one year after the intervention would be useful to assess the long-term effects of zinc on kidney function and side effects.

The effect of the community midwifery model on maternal and newborn health service utilization and outcomes in Busia County of Kenya: a quasi-experimental study

BackgroundPoor women in hard-to-reach areas are least likely to receive healthcare and thus carry the burden of maternal and perinatal mortality from complications of childbirth. This study evaluated the effect of an enhanced community midwifery model on skilled attendance during pregnancy/childbirth as well as on maternal and perinatal outcomes against the backdrop of protracted healthcare workers’ strikes in rural Kenya.MethodsThe study used a quasi-experimental (one-group pretest-posttest) design. The study spanned three time periods: December 2016-February 2017 when doctors were on strike (P1), March-May 2017 when no healthcare providers were on strike (P2), and June-October 2017 when nurses/midwives were on strike (P3), which was also the period when the project enhanced the capacity of community midwives (CMs) to provide services at the community level. Analysis entailed comparison of frequencies/means of maternal and newborn health service utilization data across the three periods.ResultsThe monthly average number of clients obtaining services from CMs across the three time periods was: first antenatal care (ANC) (P1-1.8, P2-2.3, P3-9.9), fourth ANC (P1-1.4, P2-1.0, P3-7.1), skilled birth (P1-1.5, P2-1.7, P3-13.1) and the differences in means were statistically significant (p < 0.05). Over the period, the monthly average number of clients obtaining services from health facilities was: first ANC (P1-55.7, P2-70.8, P3-4.0), fourth ANC (P1-29.6, P2-38.1, P3-1.2) and skilled birth (P1-63.1, P2-87.4, P3-5.6), p < 0.05. There were no statistically significant differences in the average number of clients obtaining services from CMs or health facilities between P1 and P2 (p > 0.05). There was, however, a statistically significant increase in the average number of clients obtaining services from CMs in P3 accompanied by a statistically significant decline in the average number of clients obtaining services from health facilities (p < 0.05). First ANC increased by 68%, fourth ANC by 75%, skilled births by 68%, and postnatal care by 33% in P3 (p < 0.0001). There was a non-significant decline in macerated stillbirths and neonatal deaths in P3.ConclusionsThe findings underscore the importance of integrating community-level health service providers (CMs and health volunteers) into the primary health care system to complement service delivery according to their level of expertise, especially in low-resource settings.

Smartphone-Delivered Progressive Muscle Relaxation for the Treatment of Migraine in Primary Care: A Randomized Controlled Trial.

Scalable, accessible forms of behavioral therapy for migraine prevention are needed. We assessed the feasibility and acceptability of progressive muscle relaxation (PMR) delivered by a smartphone application (app) in the Primary Care setting. This pilot study was a non-blinded, randomized, parallel-arm controlled trial of adults with migraine and 4+ headache days/month. Eligible participants spoke English and owned a smartphone. All participants were given the RELAXaHEAD app which includes an electronic headache diary. Participants were randomized to receive 1 of the 2 versions of the app-one with PMR and the other without PMR. The primary outcomes were measures of feasibility (adherence to the intervention and diary entries during the 90-day interval) and acceptability (satisfaction levels). We conducted exploratory analyses to determine whether there was achangein Migraine Disability Assessment Scale (MIDAS) scores or a changein headache days. Of 139 participants (77 PMR, 62 control), 116 (83%) were female, mean age was 41.7±12.8 years. Most patients 108/139 (78%) had moderate-severe disability. Using a 1-5 Likert scale, participants found the app easy to use (mean 4.2±0.7) and stated that they would be happy to engage in the PMR intervention again (mean 4.3±0.6). For the first 6weeks, participants practiced PMR 2-4days/week. Mean per session duration was 11.1±8.3minutes. Relative to the diary-only group, the PMR group showed a greater non-significant decline in mean MIDAS scores (-8.7 vs -22.7, P=.100) corresponding to a small-moderate mean effect size (Cohen's d=0.38). Smartphone-delivered PMR may be an acceptable, accessible form of therapy for migraine. Mean effects show a small-moderate mean effect size in disability scores.