Crime and punishment in Saudi Arabia: Lashing, imprisonment, and other unusual punishments.

OBJECTIVE: In this paper, we examine the antecedents of the sanctions of lashing and imprisonment for juveniles in Saudi Arabia. PARTICIPANTS AND SETTING: The current study examined 437 court cases and files across several court systems in Saudi Arabia to determine the extent to which justice-involved youth are punished. The data were drawn from hundreds of court files and records received from several court systems in Saudi Arabia spanning 2010 to 2015. METHODS: We tested several predictor variables on sentence type, number of lashes, and prison length. We employed binary logistic regression to examine sentence type, while we employed negative binomial analysis to examine the second and third dependent variables, number of lashes and length of prison sentence, respectively. RESULTS: We found that juveniles processed in juvenile court were more likely to receive more lenient sentences than juveniles tried in the general court system. In addition, older juveniles received harsher sentences (flogging and imprisonment) than younger juveniles (flogging or imprisonment), those who committed multiple offenses received more lashes than those who committed a single offense, and those who had both juvenile and adult criminal associates received more lashes than those who had only juvenile criminal associates. Moreover, the number of presiding judges influenced the severity of punishment: justice-involved youth who were tried by a single judge received fewer lashes than justice-involved youth who were tried by three or more judges. Lastly, justice-involved youth tried by a lone judge were less likely to be sentenced to a longer prison term than those tried by three or more judges. However, justice-involved youth tried by two judges received an even longer prison term than those tried by three or more judges. CONCLUSION: About one-half of all rulings examined in the current study were presided over by a lone judge. While punishments imposed by lone judges were not as severe as those imposed by two judges or three or more judges, Saudi judges wield tremendous power over their fellow citizens, more so because there are no jury trials in the Kingdom. We therefore recommend that judicial training emphasize a "do no harm" principle in sentencing. Because a two-judge panel generally imposes a harsher sentence than a panel with three or more judges, we recommend an extensive examination of the country's prior judicial rulings presided over by two judges to understand why they are more likely to issue harsher sentences than lone judges or three- or four-judge panels. The findings would lead to the development of sentencing guidelines to curb arbitrary sentencing and reverse the generally unpredictable sentence lengths imposed on justice-involved youth.

Immigration Politics and Policymaking in the USA (2017-2021): Examining the Effect of Geopolitics on Public Attitude Towards Immigration Policies.

Previous attitudinal studies on immigration in the USA largely focus on the predictors of anti-immigration sentiments compared to examining immigration policies. The dearth of scientific enquiry about the latter necessitated the present study. By analyzing individual-level data (n = 1018) obtained from the Public Religion Research Institute (PRRI), we assess the effect of geopolitics-red and blue states and other factors on public attitude towards six immigration policies in the USA (2017-2021). Overall, the results indicate a null relationship between geopolitics and public attitude towards immigration policies. Additionally, we observed several sociodemographic factors, such as age, political ideology, party affiliation, and region, influence public attitude towards immigration policies. Based on these results, it is recommended that immigration policies formulated and implemented in the USA must be based on empirical evidence and not sentiments.

Exploration of factors influencing court outcomes in cases involving minors as victims in Ghana.

BACKGROUND: The factors that influence positive court outcomes for cases of child sexual abuse (CSA) have been studied in other contexts but very few such studies exist for Sub-Saharan countries. Knowledge of how such cases fare in these court systems is, however, important for a global assessment of such outcomes. OBJECTIVE: The study explored the predictive effect of the victim, complainant; offender and offence characteristics, and length of the trial on case disposition and dropout. METHODS, PARTICIPANTS AND SETTING: Three hundred and eighty-nine (389) closed court files related to child sexual abuse in Ghana were reviewed and analyzed. RESULTS: The findings show that the number of court sittings (length of trial) and complainant characteristics predict negative outcomes for CSA cases in Ghana. Specifically, convictions were less likely to occur where caregivers were the complainants (OR = 0.45), and when there were longer court sittings (OR = 0.95). Victim, offender, and offence characteristics, however, did not influence case outcomes. CONCLUSIONS: This study is one of the first studies using actual court data to predict the outcome of cases in CSA in Ghana, and makes recommendations for the support of children and caregivers through the court process.

Global Analysis and Optimal Control Model of COVID-19.

COVID-19 remains the concern of the globe as governments struggle to defeat the pandemic. Understanding the dynamics of the epidemic is as important as detecting and treatment of infected individuals. Mathematical models play a crucial role in exploring the dynamics of the outbreak by deducing strategies paramount for curtailing the disease. The research extensively studies the SEQIAHR compartmental model of COVID-19 to provide insight into the dynamics of the disease by underlying tailored strategies designed to minimize the pandemic. We first studied the noncontrol model's dynamic behaviour by calculating the reproduction number and examining the two nonnegative equilibria' existence. The model utilizes the Castillo-Chavez method and Lyapunov function to investigate the global stability of the disease at the disease-free and endemic equilibrium. Sensitivity analysis was carried on to determine the impact of some parameters on R 0. We further examined the COVID model to determine the type of bifurcation that it exhibits. To help contain the spread of the disease, we formulated a new SEQIAHR compartmental optimal control model with time-dependent controls: personal protection and vaccination of the susceptible individuals. We solved it by utilizing Pontryagin's maximum principle after studying the dynamical behaviour of the noncontrol model. We solved the model numerically by considering different simulation controls' pairing and examined their effectiveness.

Immigrants, Crime, and the American Dream: Testing a Segmented Assimilation Theory of Crime.

The immigrant-crime relationship is often misunderstood and highly complex. To date, criminological research has largely ignored theory testing of this relationship. This paper examines the extant literature on intergenerational offending amongst immigrant youth and subsequently tests whether the segmented assimilation theory- a theory borrowed from the interdisciplinary social sciences- adequately explains immigrant offending. The study uses data (N = 1,267) from the Pathways to Desistance Study (PTD) to examine intergenerational differences in changes to offending between immigrant youth and the native-born. The analyses largely reveal that the theory, based on its original assumptions, fails to adequately explain youth offending, and that the models provide more support for the straight-line theory of assimilation in regards to delinquency. Limitations and recommendations are discussed and proffered, respectively.

Mathematical modelling of the epidemiology of COVID-19 infection in Ghana.

In this paper, Covid-19 patients with self-immunity is incorporated in the Susceptible-Exposed-Infected-Quarantined-Recovered ( S E I Q R ) model is applied to describe the epidemiology of Covid-19 infection in Ghana. Based on data on the epidemiology of the Covid-19 infection in Ghana, we observed that, on an average, three persons contract the Covid-19 infection from an infected person daily based using the basic reproductive number ( R o ) derived from the SEIQR model. In addition, the threshold condition for the long term stability of the Covid-19 infection in Ghana is derived from this model. Based on the Dulac criterion, it was observed that for a long period of time the epidemiology of Covid-19 in Ghana will be under control. Again, we observed that both the transmission rate natural death rate of a person in the various classes mostly influence the spread of Covid-19 infection followed by the exposed rate from exposure class to the infected class, then the rate at which an infected person is quarantined and finally, the rate at an exposed person is quarantined. On the other hand, the rate at which an exposed person recovers from his/her have least influence on the spread of Covid-19 infection in the country. Nevertheless, the rates of birth, transmission of Covid-19 infection to a susceptible person, exposure to Covid-19 infection and Covid-19 patient who is quarantined by the facilities provided by the Ghana Health Service ( G H S ) are in direct relationship with R o . However, the rates at which a quarantiner dies from a Covid-19 infection, an infected person dies from a Covid-19 infection, natural death from each class and the recoveries from an infected class, exposed class and quarantined class are in relationship with R o .

Nurses' and midwives' perspectives on participation in national policy development, review and reforms in Ghana: a qualitative study.

BACKGROUND: The World Health Organization has admonished member countries to strive towards achieving universal health coverage (UHC) through actionable health policies and strategies. Nurses and midwives have instrumental roles in achieving UHC via health policy development and implementation. However, there is a paucity of empirical data on nurses and midwives' participation in policy development in Ghana. The current study explored nurses and midwives' participation in policy development, reviews and reforms in Ghana. METHODS: A qualitative descriptive exploratory design was adopted for this study. One-on-one individual interviews were conducted after 30 participants were purposefully selected. Data was audiotaped with permission, transcribed and analyzed inductively using the content analysis procedures. RESULTS: Two main themes emerged from the data: participation in policy development and perspectives on policy reviews and reforms. The findings showed that during health policy development and reviews, nurses in Ghana were overlooked and unacknowledged. Policy reforms regarding bridging the pre-service preparation gap, staff development and motivation mechanisms and influence on admission into nursing schools were raised. CONCLUSION: The authors concluded that nurses and midwives are crucial members of the healthcare systems and their inputs in policy development and reviews would improve health delivery in Ghana.

Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial.

BACKGROUND: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to established guidelines. Therefore, we aimed to investigate the efficacy of the combination drug device Amikacin Inhale as an adjunctive therapy to intravenous standard-of-care antibiotics for pneumonia caused by Gram-negative pathogens in intubated and mechanically ventilated patients. METHODS: INHALE was a prospective, double-blind, randomised, placebo-controlled, phase 3 study comprising two trials (INHALE 1 and INHALE 2) done in 153 hospital intensive-care units in 25 countries. Eligible patients were aged 18 years or older; had pneumonia that had been diagnosed by chest radiography and that was documented as being caused by or showing two risk factors for a Gram-negative, multidrug-resistant pathogen; were intubated and mechanically ventilated; had impaired oxygenation within 48 h before screening; and had a modified Clinical Pulmonary Infection Score of at least 6. Patients were stratified by region and disease severity (according to their Acute Physiology and Chronic Health Evaluation [APACHE] II score) and randomly assigned (1:1) via an interactive voice-recognition system to receive 400 mg amikacin (Amikacin Inhale) or saline placebo, both of which were aerosolised, administered every 12 h for 10 days via the same synchronised inhalation system, and given alongside standard-of-care intravenous antibiotics. All patients and all staff involved in administering devices and monitoring outcomes were masked to treatment assignment. The primary endpoint, survival at days 28-32, was analysed in all patients who received at least one dose of study drug, were infected with a Gram-negative pathogen, and had an APACHE II score of at least 10 at diagnosis. Safety analyses were done in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, numbers NCT01799993 and NCT00805168. FINDINGS: Between April 13, 2013, and April 7, 2017, 807 patients were assessed for eligibility and 725 were randomly assigned to Amikacin Inhale (362 patients) or aerosolised placebo (363 patients). 712 patients received at least one dose of study drug (354 in the Amikacin Inhale group and 358 in the placebo group), although one patient assigned to Amikacin Inhale received placebo in error and was included in the placebo group for safety analyses. 508 patients (255 in the Amikacin Inhale group and 253 in the placebo group) were assessed for the primary endpoint. We found no between-group difference in survival: 191 (75%) patients in the Amikacin Inhale group versus 196 (77%) patients in the placebo group survived until days 28-32 (odds ratio 0·841, 95% CI 0·554-1·277; p=0·43). Similar proportions of patients in the two treatment groups had a treatment-emergent adverse event (295 [84%] of 353 patients in the Amikacin Inhale group vs 303 [84%] of 359 patients in the placebo group) or a serious treatment-emergent adverse event (101 [29%] patients vs 97 [27%] patients). INTERPRETATION: Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia. FUNDING: Bayer AG.

Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study.

BACKGROUND: Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP. METHODS: RISE-IIP was a double-blind, randomised, placebo-controlled study done at 65 pulmonary hypertension and interstitial lung disease centres in 19 countries to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Eligible patients were adults (aged 18-80 years) diagnosed with idiopathic interstitial pneumonia (as per American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines), forced vital capacity (FVC) of at least 45%, 6MWD of 150-450 m, WHO functional classes II-IV, precapillary pulmonary hypertension confirmed by right heart catheterisation, systolic blood pressure of at least 95 mm Hg, and no signs or symptoms of hypotension. Patients were randomly allocated (1:1) using an interactive voice and web response system to riociguat (0·5-2·5 mg three times daily) or placebo for 26 weeks (main study), after which they could enter an open-label extension in which all patients received riociguat. The primary endpoint was change in 6-min walking distance (6MWD) in the intention-to-treat population. Prespecified safety variables included adverse events and serious adverse events, laboratory parameters, and adverse events of special interest (haemoptysis and symptomatic hypotension), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02138825. FINDINGS: Between June 4, 2014, and May 5, 2016, we enrolled 229 participants. After the exclusion of 82 participants, 147 were randomly allocated to treatment (73 to riociguat, 74 to placebo). The study was terminated early (median treatment duration 157 days [range 6-203]) at the request of the data monitoring committee owing to increased serious adverse events (main study: 27 [37%] of 73 participants in the riociguat group vs 17 [23%] of 74 in the placebo group) and mortality in patients receiving riociguat, and the absence of efficacy signals in the riociguat group. 11 patients died in the main study (eight in the riociguat group, three in the placebo group), and nine died in the extension phase (one in the riociguat group, eight in the former placebo group; all received riociguat). In the main study, the most common adverse events were peripheral oedema (16 [22%] of 73 in the riociguat group vs seven [9%] of 74 in the placebo group) and diarrhoea (11 [15%] vs seven [9%]). The most common serious adverse events were worsening of interstitial lung disease (main study: six [8%] of 73 in the riociguat group vs five [7%] of 74 in the placebo group) and pneumonia (four [5%] vs one [1%]). Riociguat did not improve 6MWD versus placebo at 26 weeks (least-squares mean difference 21 m; 95% CI -9 to 52). INTERPRETATION: In patients with PH-IIP, riociguat was associated with increased serious adverse events and mortality, and an unfavourable risk-benefit profile. Riociguat should not be used in patients with PH-IIP. FUNDING: Bayer AG and Merck & Co.

Novel bioerodable eluting-spacers for radiotherapy applications with in situ dose painting.

OBJECTIVE: To investigate feasibility of using bioerodable/bioerodible spacers (BES) over biodegradable spacers (BDS) loaded with gold nanoparticles for radiotherapy applications with in situ dose-painting, and to explore dosimetric impact on dose enhancement ratio of different radioisotopes. METHODS: Analytical models proposed were based on experimentally reported erosion rate constant (k 0 = 5. 5E-7 kgm- 2s- 1 ) for bioerodible polymeric matrix. An in vivo determined diffusion coefficient (2.2E-8 cm2/s) of 10 nm gold nanoparticles (AuNP) of concentration 7 mg/g was used to estimate diffusion coefficient of other AuNP sizes (2, 5, 14 nm) using the Stoke-Einstein diffusion equation. The corresponding dose enhancement factors (DEF) were used to study dosimetric feasibility of employing AuNP-eluting BPS for radiotherapy applications. RESULTS: The results showed AuNP release period from BES was significantly shorter (116 h) compared to BDS (more than a month) reported previously. The results also agree with reported Hopfenberg equation for a cylindrical matrix undergoing surface erosion. The DEF at tumour distance 5 mm for Cs-131 (DEF > 2.2) greater than that of I-125 (DEF > 2) and Pd-103 (DEF ≥ 2) could be achieved for AuNP sizes (2, 5, 10, and 14 nm) respectively. CONCLUSION: Our findings suggested that BES could be used for short-lived radioisotopes like Pd-103 and Cs-131 in comparison to eluting BDS which is feasible for long-lived radioisotopes like I-125. ADVANCES IN KNOWLEDGE: The study provides scientific basis for development of new generation eluting spacers viable for enhancing localized tumour dose. It concludes that BES gives higher DEF for Cs-131, and good candidate for replacing conventional fiducials/spacers.

Trust and Confidence in Media and Criminal Justice Institutions.

In every society, the main purpose of the criminal justice system is to maintain social order and ensure that citizens comply with the law. To do this effectively, the police and court systems need citizen cooperation and obedience, and willingness to assist with criminal investigations and report crimes to the police. The purpose of this study is to examine the association between confidence in the media and confidence in the criminal justice institutions in South Africa. The study tests two objectives: to assess South Africans' level of confidence in the police and courts, and to determine whether citizens' levels of confidence in both the print and televised media will influence their levels of confidence in the police, courts, and in the criminal justice system in general. Utilizing data from the World Values Survey, results reveal a significant and positive relationship between confidence in the media and confidence in the criminal justice institutions. Policy implications of this observation are discussed.

Misconduct Within the "Four Walls": Does Organizational Justice Matter in Explaining Prison Officers' Misconduct and Job Stress?

Primarily, this article examines the role of organizational justice in understanding prison officers' behavior. The authors surveyed 169 correctional officers across five correctional facilities in Ghana to explore the role of three organizational justice dimensions in prison misconduct and job stress. Results from the negative binomial and ordinal logistic analyses revealed the significant contributions of two dimensions of organizational justice in explaining misconduct and stress among officers. Officers who had higher perceptions of distributive fairness and interaction in the organization had lower odds of receiving misconduct-related complaints. Also, greater interaction was found to be associated with reduced job stress among prison officers. In addition, several officers' characteristics were found to predict the number of times officers received misconduct complaints.

Fearfulness in the Community: Empirical Assessments of Influential Factors.

Fear of crime has been well studied; however, there has yet not been widespread consideration of the potential impact of both individual- and neighborhood-level factors on residents' level of fear of crime. From a logistic-regression analytical standpoint, the present study empirically explores the contribution of several factors in explaining residents' propensity for being fearful of crime. Precisely, the study tests the applicability and generalizability of three theoretical perspectives of fear of crime in the Ghanaian context and examines the effects of residents' attitudes toward the police on their levels of fear of crime. Using large-scale cross-sectional data collected on more than 1,000 residents from 25 neighborhoods in Ghana, the results demonstrate significant predictive effects of both individual- and neighborhood-level factors on citizens' rate of fearfulness. Findings from this study have both theoretical and practical implications, and provide important insights for the police to reduce levels of fear of crime in the community.

Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications.

Nanoparticle-based radiosensitization of cancerous cells is evolving as a favorable modality for enhancing radiotherapeutic ratio, and as an effective tool for increasing the outcome of concomitant chemoradiotherapy. Nevertheless, delivery of sufficient concentrations of nanoparticles (NPs) or nanoparticle-based radiosensitizers (NBRs) to the targeted tumor without or with limited systemic side effects on healthy tissues/organs remains a challenge that many investigators continue to explore. With current systemic intravenous delivery of a drug, even targeted nanoparticles with great prospect of reaching targeted distant tumor sites, only a portion of the administered NPs/drug dosage can reach the tumor, despite the enhanced permeability and retention (EPR) effect. The rest of the targeted NPs/drug remain in systemic circulation, resulting in systemic toxicity, which can decrease the general health of patients. However, the dose from ionizing radiation is generally delivered across normal tissues to the tumor cells (especially external beam radiotherapy), which limits dose escalation, making radiotherapy (RT) somewhat unsafe for some diseased sites despite the emerging development in RT equipment and technologies. Since radiation cannot discriminate healthy tissue from diseased tissue, the radiation doses delivered across healthy tissues (even with nanoparticles delivered via systemic administration) are likely to increase injury to normal tissues by accelerating DNA damage, thereby creating free radicals that can result in secondary tumors. As a result, other delivery routes, such as inhalation of nanoparticles (for lung cancers), localized delivery via intratumoral injection, and implants loaded with nanoparticles for local radiosensitization, have been studied. Herein, we review the current NP delivery techniques; precise systemic delivery (injection/infusion and inhalation), and localized delivery (intratumoral injection and local implants) of NBRs/NPs. The current challenges, opportunities, and future prospects for delivery of nanoparticle-based radiosensitizers are also discussed.

Fear of Crime in the Sanctuary: Comparing American and Ghanaian University Students' Fearfulness.

While much is known about fear of crime in the West, little is known about how fearfulness of crime develops in non-Western societies, especially among university students. Representing the first attempt to empirically compare levels of fear of crime between Ghanaian and U.S. college students, this article examined students' levels of fear of crime on campus, and tested the applicability of two evolving models of fear of crime-the vulnerability and reassurance models-using comparative data. The general finding is that Ghanaian and U.S. college students differ in terms of their rates of fearfulness on campus. This significant difference adds to the already existing differences between the two countries.

Crime Reporting Behavior: Do Attitudes Toward the Police Matter?

Police researchers have long argued that favorable evaluations of the police eventually lead to citizens' willingness to cooperate with the police. However, this assumption has barely been studied empirically. The current study examines the association between attitudes toward the police and crime reporting behavior of victims. Furthermore, the study explores the influence of victims' characteristics on their decisions to report crime to the police. Using field data originally collected in Ghana, the study found that victims' levels of confidence in the police and satisfaction with police work positively predict their decisions to report sexual assault and robbery to the police. Moreover, findings revealed that age, marital status, and employment status are important predictors of victims' reporting behavior. Several practical and theoretical implications of the results are discussed.

Modeling gold nanoparticle-eluting spacer degradation during brachytherapy application with in situ dose painting.

OBJECTIVE: To investigate the dosimetric impact of slow vs burst release of gold nanoparticles (GNPs) from biodegradable brachytherapy spacers loaded with GNPs, which has been proposed to increase therapeutic efficacy during brachytherapy application with in situ dose painting. METHODS: Mathematical models were developed based on experimental data to study the release of GNPs from a spacer designed with poly(lactic-co-glycolic acid) polymer. The models addressed diffusion controlled-release process and poly(lactic-co-glycolic acid) degradation kinetics that were used to determine GNP concentration profiles in tumour and the corresponding dose enhancement. RESULTS: The results show a significant delay of GNP diffusion in the tumour in comparison to burst release assumed in previous studies. The model for diffusion controlled-release process and the model for combined processes of both diffusion and polymer degradation indicated that it may take about 25 and 45 days, respectively, for all GNPs to release from the spacer. Based on tumour concentration profiles, a significant dose enhancement factor (>2) could be attained at a tumour distance of 5 mm from a spacer loaded with 2-, 5- and 10-nm GNP sizes. CONCLUSION: The results highlight the need to account for the slow release of GNPs from spacers and polymer biodegradation in research development of the GNP-eluting spacers. The findings suggest the use of radioisotopes with longer half-lives, such as iodine-125, in comparison with others with shorter half-lives such as Pd-103 and Cs-131. Advances in knowledge: The study provides a scientific platform and basis for research development of GNP-eluting spacers that can be used during brachytherapy to boost dose to tumour subvolumes, towards enhancing therapeutic efficacy. It concludes that the use of iodine-125 would be more feasible.

Smart Radiation Therapy Biomaterials.

Radiation therapy (RT) is a crucial component of cancer care, used in the treatment of over 50% of cancer patients. Patients undergoing image guided RT or brachytherapy routinely have inert RT biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to "smart" RT biomaterials, designed to do more than 1 function. Such smart biomaterials include next-generation fiducial markers, brachytherapy spacers, and balloon applicators, designed to respond to stimuli and perform additional desirable functions like controlled delivery of therapy-enhancing payloads directly into the tumor subvolume while minimizing normal tissue toxicities. More broadly, smart RT biomaterials may include functionalized nanoparticles that can be activated to boost RT efficacy. This work reviews the rationale for smart RT biomaterials, the state of the art in this emerging cross-disciplinary research area, challenges and opportunities for further research and development, and a purview of potential clinical applications. Applications covered include using smart RT biomaterials for boosting cancer therapy with minimal side effects, combining RT with immunotherapy or chemotherapy, reducing treatment time or health care costs, and other incipient applications.

Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study.

BACKGROUND: Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction. METHODS AND RESULTS: Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (-6.1±1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L·min(-1)·m(-2); 95% confidence interval, 0.2-0.5; P=0.0001) and stroke volume index (5.2 mL·m(-2); 95% confidence interval, 2.0-8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (-46.6 dynes·s(-1)·cm(-5); 95% confidence interval, -89.4 to -3.8; P=0.03) and systemic vascular resistance (-239.3 dynes·s(-1)·cm(-5); 95% confidence interval, -363.4 to -115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups. CONCLUSIONS: Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01065454.

The Combined Effect of Nursing Support and Adverse Event Mitigation on Adherence to Interferon Beta-1b Therapy in Early Multiple Sclerosis: The START Study.

There is limited clinical evidence on the impact of nurse support and adverse event (AE) mitigation techniques on adherence to interferon beta-1b (IFNß-1b) therapy in multiple sclerosis (MS) in a real-world setting. The aim of the Success of Titration, analgesics, and BETA nurse support on Acceptance Rates in MS Treatment (START) trial was to assess the combined effect of titration, analgesics, and BETA (Betaseron Education, Training, Assistance) nurse support on adherence to IFNß-1b therapy in patients with early-onset MS and to evaluate safety. Participants were instructed to titrate IFNß-1b and use analgesics to minimize flu-like symptoms. All received BETA nurse follow-up at frequent intervals: live training, two telephone calls during the first month of therapy, and monthly calls thereafter. Participants were considered adherent if they took at least 75% of the total prescribed doses over 12 months (≥75% compliance). Safety was monitored via reported AEs and laboratory test results. Participants who took at least one IFNß-1b dose over 12 months were analyzed (N = 104); 73.8% of participants completed the study. The mean age of participants was 37.2 years; 72.1% were women and 78.8% were white. Ninety participants had relapsing-remitting MS and 14 had clinically isolated syndrome. The mean compliance rate, reported for 96 participants with complete dose interruption records, was 84.4%. At 12 months, 78.1% of participants were considered adherent. The serious adverse event rate was 9.6%; most events were unrelated to therapy. Thus in the START study, in which participants received nursing support combined with dose titration and use of analgesics, the majority of participants were adherent to therapy.