Communication lessons learned from the 2017 measles-rubella campaign in India: perspectives from vaccine decision-makers.

In 2017, to reduce the burden of measles and rubella, a nation-wide measles-rubella campaign was launched in India. Despite detailed planning efforts that involved many stakeholders, vaccine refusal arose in several communities during the campaign. As strategic health communication and promotion is critical in any vaccine campaign, we sought to document lessons learned from the 2017 MR campaign from a strategic health communication and promotion perspective to capture lessons learned. To inform future campaigns, we conducted in-depth interviews through a perspective that is not usually captured, that of government and civil society stakeholders that had experience in vaccine campaign implementation (n = 21). We interviewed stakeholders at the national level and within three states that had diverse experiences with the campaign. Three key themes related to strategic health communication and promotion emerged: the importance of sensitizing communities at all levels through relevant and timely information about the vaccine and the vaccine campaign, leveraging key influencers to deliver tailored messaging about the importance of vaccines and mitigating vaccine misinformation rapidly. Our study findings have important implications for health communication and promotion research related to vaccine campaigns. The field must continue to enhance vaccine campaign efforts by identifying important health communication and promotion factors, including the importance of sensitization, trusted messengers that use tailored messaging and mitigating misinformation, as vaccine campaigns are crucial in improving vaccine acceptance.

Measles and rubella are diseases that cause sickness and death. Both are preventable as there are safe and effective vaccines available. Measles and rubella are significant in India. These vaccines are generally delivered to the public through vaccine campaigns. A measles­rubella vaccine campaign was implemented in 2017. In this study, we interviewed 21 government and civil society stakeholders that are involved in vaccine campaigns in India to capture lessons learned. We were interested in understanding how vaccine campaigns could be improved through health communication and promotion efforts. Stakeholders suggested to use trusted community members to inform people about the vaccine campaign, and that it was important for trusted community leaders to dispel rumors about vaccines quickly. To increase vaccine acceptance, it is critical that health communication and promotion efforts target concerns that people may have about the vaccine as well as the vaccine campaign.

Community child psychiatric medication experiences measured by an internet-based, prospective parent survey of retail pharmacy customers.

One thousand five hundred parents filling a psychiatric prescription for their 6-18 year old child with a multi-state retail pharmacy chain received a single mailed invitation to complete a detailed online survey. 276 parents responded (18.4%). 60% of children on medications had a parent rated CBCL scale score in the clinically significant range at enrollment (T score ≥65), with a similar frequency of clinically significant CBCL scores through 15 months of survey followup. 47% of medication regimens were noted to be causing persistent side effects. This simple community based data collection method can offer a unique way to investigate naturalistic treatment outcomes.

A prospective comparison of cardiac imaging using intracardiac echocardiography with transesophageal echocardiography in patients with atrial fibrillation: the intracardiac echocardiography guided cardioversion helps interventional procedures study.

BACKGROUND: The Intracardiac Echocardiography Guided Cardioversion Helps Interventional Procedures study evaluated the concordance of intracardiac echocardiography (ICE) with transesophageal echocardiography (TEE) in patients with atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF undergoing right heart catheterization underwent left atrium (LA) and interatrial septal (IAS) imaging by TEE and ICE. A blinded comparison of the 2 modalities was performed at a core laboratory. Ninety-five patients aged 58 ± 12 years completed the study. The LA was profiled in all patients with both techniques, and concordance for image quality was 96%. LA appendage (LAA) imaging was achieved in 85% with ICE and 96% with TEE. There was no difference in the presence of spontaneous echo contrast between ICE and TEE during LA imaging, but there was a trend toward a greater incidence in the LAA with TEE (P = 0.109). Intracardiac thrombus was uncommonly seen (TEE, 6.9%; ICE, 5.2%). The concordance for the presence or absence of thrombus was 97% in the LA and 92% in the LAA, but the latter was detected more frequently with TEE. IAS imaging was achieved in 91% with ICE and in 97% with TEE (P = 0.177). Concordance for patent foramen ovale and atrial septal aneurysms was 100% and 96%, respectively. A negative ICE examination was associated with absence of dense echo contrast or thrombus on TEE in 86%. CONCLUSIONS: This study provides validation for the use of ICE for LA and IAS imaging. ICE imaging was less sensitive compared to TEE for LAA thrombus identification. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00281073.

Are there sex differences in affective modulation of spinal nociception and pain?

UNLABELLED: Sex differences in the processing and experience of emotion exist. The present study examined whether sex differences in emotion lead to sex differences in affective modulation of pain and spinal nociception (assessed by nociceptive flexion reflex, NFR). Participants were healthy men (n = 47) and women (n = 73). Prior to affective modulation testing, electrocutaneous pain sensitivity was assessed (NFR threshold, pain threshold, pain tolerance). Affective modulation of pain and NFR was then assessed by presenting pictures that vary in emotional valence and arousal (mutilation, attack, death, neutral, families, adventure, erotica) during which suprathreshold electrocutaneous stimulations were delivered. Subjective emotional reactions were assessed after every picture, and nociceptive reactions were assessed after every suprathreshold stimulus. Results indicated women had greater pain sensitivity and also responded more negatively to attack pictures and less positively to erotic pictures. But despite these differences, affective modulation of pain/NFR was not moderated by sex: erotic pictures inhibited pain/NFR and mutilation pictures enhanced pain/NFR. Together, this implies subjective emotional experience does not completely mediate picture-evoked modulation of pain/NFR, a supposition that was further supported by exploratory analyses that demonstrated picture-evoked modulation of pain/NFR was present even after controlling for intra- and inter-individual differences in emotional reactions to pictures. Implications and limitations of these findings are discussed. PERSPECTIVE: Evidence suggests that women are more sensitive to experimental and clinical pain, but the mechanisms contributing to these sex differences are poorly understood. Affective processes are known to play a role in regulating pain signaling and pain experience; therefore, the present study examined whether sex differences in affective experience contribute to sex differences in pain. Results indicate that in healthy individuals affective processes may not contribute to sex differences in pain.

Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies.

AIMS: The AFFIRM and RACE studies showed that rate control is an acceptable treatment strategy for atrial fibrillation (AF). We examined whether strict rate control offers benefit over more lenient rate control. METHODS AND RESULTS: We compared the outcome of patients enrolled in the rate-control arms of AFFIRM and RACE, using data from patients who met a composite of overlapping inclusion and exclusion criteria. We evaluated 1091 patients, 874 from AFFIRM and 217 from RACE. In AFFIRM, the rate-control strategy aimed for a resting heart rate < or =80 bpm and heart rate during daily activity of < or =110 bpm. In RACE, a more lenient approach was taken: resting heart rate <100 bpm. Primary endpoint was a composite of mortality, cardiovascular hospitalization, and myocardial infarction. Mean heart rate across all follow-up visits for patients in AF was lower in AFFIRM (76.1 vs. 83.4 bpm). Event-free survival for the occurrence of the primary endpoint did not differ (64% in AFFIRM vs. 66% in RACE). Patients with mean heart rates during AF within the AFFIRM (< or =80) or RACE (<100) criteria had a better outcome than patients with heart rates > or =100 (hazard ratios 0.69 and 0.58, respectively, for < or =80 and <100 compared with > or =100 bpm). CONCLUSION: Stringency of the approach to rate control, based on the comparison of the AFFIRM and RACE studies, was not associated with an important difference in clinical events.

Perceived effects on patients' health of participation in the atrial fibrillation follow-up investigation of rhythm management study.

BACKGROUND: Patients' views about participation in clinical trials have been explored using end-of-study questionnaires for various disease entities. However, little is known about why individuals with atrial fibrillation (AF) choose to participate in clinical trials or how they view their research experience. Understanding these perceptions should provide valuable information for future studies in developing methods to enhance enrollment, optimize adherence to therapies, and maximize patient retention. METHODS: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a randomized trial of rate-control versus rhythm-control for the management of AF. This descriptive ancillary study used a 7-item questionnaire comprising closed and open-ended items that explored: (1) perceptions of benefits from participation, (2) motivation for enrolling, and (3) satisfaction with research staff and operations. RESULTS: A total of 741/1,032 participants (72%) at 34 of 213 participating AFFIRM sites responded, representing 18% of the 4,060 patients enrolled. The mean follow-up of these respondents was 3.8 +/- 1.1 years. Most respondents (91%) felt that they received enough information about AFFIRM before enrolling and that the results would benefit themselves (88%) and others (91%). Most respondents felt study participation improved awareness about AF (90%) and facilitated coordination of their healthcare (89%). Virtually all were satisfied with information received from AFFIRM personnel (96%), and most (98%) reported that they had received "good care." Responses were similar between randomization groups (rate-control or rhythm-control) and between those younger than 65 years and those 65 years or older. Participants in sinus rhythm at last follow-up were more likely to believe that their medical care in AFFIRM was better than what they would otherwise have received, and were more likely to perceive their treatment course as entailing fewer emergency room visits, hospitalizations, and doctor visits. Regularly scheduled appointments and ongoing availability of staff to answer questions appeared to increase participants' confidence and reduce anxiety. CONCLUSIONS: Patients enrolled in a long-term clinical trial for management of AF were overwhelmingly satisfied with participation.

Atrial fibrillation among African Americans, Hispanics and Caucasians: clinical features and outcomes from the AFFIRM trial.

UNLABELLED: The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study concluded that rate control with anticoagulation was equivalent overall to rhythm control with cardioversion for long-term survival and that anticoagulation reduced the risk of stroke. We compared baseline and follow-up data for three ethnic groups: Caucasians (n=3,599), African Americans (n=265) and Hispanics (n=132). Caucasians were older and more likely male, African Americans were more likely female and hypertensive, and Hispanics had higher prevalence of cardiomyopathy. Survival was better for rate control than rhythm control in Caucasians, equivalent in African Americans and better for rhythm control in Hispanics. Outcomes may be influenced by differential baseline characteristics, but low numbers of African Americans and Hispanics warrant caution in data interpretation. BACKGROUND: The AFFIRM study compared a rate-control strategy to a rhythm-control strategy for the treatment of atrial fibrillation (AF) in patients at high risk for stroke or death. It concluded that the rhythm-control strategy offered no survival advantage, and it also confirmed the value of anticoagulation to prevent complications of AF. Data have not previously been available for specific racial ethnic populations. METHODS: We compared baseline and follow-up data for the patients randomized to rate-control versus rhythm-control in three population groups-Caucasian, African-American and Hispanic. RESULTS: Among 4,060 total patients, 3,599 were Caucasian, 265 were African-American and 132 were Hispanic. At baseline, Caucasians were older and had a higher percentage of males, normal ejection fractions, AF as their only cardiac diagnosis, a prior antiarrhythmic drug failure and less congestive heart failure. African Americans were more likely to be female, had more hypertension and qualified for the study with a first episode of AF, compared to Caucasians. Hispanics had more cardiomyopathy at baseline than Caucasians. Overall survival in Caucasians at five years for the rate-control and rhythm-control groups was 78.9% vs. 76.4%, respectively (p=0.04); for African Americans, 79.0% vs. 69.4% (p=0.22); and for Hispanics, 66.5% vs. 83.9% (p=0.01). Overall, survival was not different between the three populations. However, lower rates of event-free survival were recorded for Hispanics and for African Americans (p=0.0182). CONCLUSIONS: Different survival rates were found for rate-control versus rhythm-control in African-American and Hispanic patients, compared to Caucasian. These findings may be influenced by differences in baseline characteristics, but must be interpreted with caution because of the small sample sizes for African-American and Hispanic participants.

Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database).

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were <65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (<65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.

Insulin resistance and preeclampsia in gestational diabetes mellitus.

OBJECTIVE: To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n = 150) and 15 months postpartum (n = 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] > or = 140 mmHg, diastolic blood pressure [DBP] > or = 90 mmHg, and at least >1+ proteinuria or >300 mg/24 h). Metabolic parameters between the groups were compared by chi2 or Fisher's exact tests and ANOVA with P < 0.05 as significant. RESULTS: A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 +/- 2.4 vs. 60.1 +/- 2.3 in, P = 0.003), were more often nulliparous (38 vs. 16%, P = 0.01), and had higher entry SBP (112 +/- 10 vs. 103 +/- 6.9 mmHg, P < 0.0001) and DBP (64 +/- 9 vs. 59 +/- 5 mmHg, P = 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n = 19) compared with the nonpreeclamptic group (n = 70). No differences in any glycemic or insulin resistance measures were found. CONCLUSIONS: Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic.

Are transthoracic echocardiographic parameters associated with atrial fibrillation recurrence or stroke? Results from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.

OBJECTIVES: The purpose of this study was to evaluate the associations of transthoracic echocardiographic parameters with recurrent atrial fibrillation (AF) and/or stroke. BACKGROUND: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, an evaluation of elderly patients with AF at risk for stroke, provided an opportunity to evaluate the implications of echocardiographic parameters in patients with AF. METHODS: Transthoracic echocardiographic measures of mitral regurgitation (MR), left atrial (LA) diameter, and left ventricular (LV) function were evaluated in the AFFIRM rate- and rhythm-control patients who had sinus rhythm resume and had these data available. Risk for recurrent AF or stroke was evaluated with respect to transthoracic echocardiographic measures. RESULTS: Of 2,474 patients studied, 457 had > or =2(+)/4(+) MR, and 726 had a LA diameter >4.5 cm. The LV ejection fraction was abnormal in 543 patients. The cumulative probabilities of at least one AF recurrence/stroke were 46%/1% after 1 year and 84%/5% by the end of the trial (> 5 years), respectively. Multivariate analysis showed that randomization to the rhythm-control arm (hazard ratio [HR] = 0.64; p < 0.0001) and a qualifying episode of AF being the first known episode (HR = 0.70; p < 0.0001) were associated with decreased risk. Duration of qualifying AF episode >48 h (HR = 1.55; p < 0.0001) and LA diameter (p = 0.008) were associated with an increased risk of recurrent AF. Recurrent AF was more likely with larger LA diameters (HR = 1.21, 1.16, and 1.32 for mild, moderate, and severe enlargement, respectively). No transthoracic echocardiographic measures were associated with risk of stroke. CONCLUSIONS: In the AFFIRM study, large transthoracic echocardiographic LA diameters were associated with recurrent AF, but no measured echocardiographic parameter was associated with stroke.

Risk of proarrhythmic events in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: a multivariate analysis.

OBJECTIVES: This study examined the risk of proarrhythmic events in patients receiving antiarrhythmic drugs for treatment of atrial fibrillation (AF) according to present-day safety guidelines. BACKGROUND: Advances in understanding the proarrhythmic risk of antiarrhythmic drugs has led to development of safety guidelines for these agents. Such guidelines were used in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. METHODS: This study was an analysis of the risk of arrhythmic events (arrhythmic death, resuscitated cardiac arrest, sustained ventricular tachycardia (VT), and torsade de pointes VT) in the antiarrhythmic drug arm of the AFFIRM study. Each time an antiarrhythmic drug was begun, it was counted as an exposure to that drug and the risk of an arrhythmic event was calculated. RESULTS: A total of 2,033 patients received 3,030 exposures to antiarrhythmic drugs. Ninety-six arrhythmic events occurred by six years. Patients with a left ventricular ejection fraction <40% had more arrhythmic events. Twelve documented cases of torsade de pointes VT were noted. The incidence of torsade de pointes was 0.6% at five years (95% confidence interval 0.32 to 1.07). CONCLUSIONS: The overall risk of adverse arrhythmic events upon exposure to antiarrhythmic drugs in the AFFIRM study was reasonably low. Strict criteria for the safe use of antiarrhythmic drugs were successful in minimizing proarrhythmic events.

Relation between achieved heart rate and outcomes in patients with atrial fibrillation (from the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] Study).

Many patients with atrial fibrillation (AF) are treated with rate control and anticoagulation. However, the relation between the degree of heart rate (HR) control and clinical outcome is uncertain. We assessed whether lower achieved HR at rest and/or lower achieved exercise HR was associated with improved prognosis, quality of life (QoL), and functional status among patients in the AFFIRM study. Patients in the rate control arm and who were in AF at baseline and 2 months were included. Patients were grouped by quartile of achieved HR at rest (44 to 69, 70 to 78, 79 to 87, 88 to 148 beats/min) and achieved exercise HR following a 6-minute walk (53 to 82, 83 to 92, 93 to 106, 107 to 220 beats/min). QoL measurements and functional status were also analyzed. Complete data were available for 680 patients for achieved HR at rest, 349 patients for achieved exercise HR, and 118 patients for QoL. Survival free from cardiac hospitalization and overall survival were not significantly different among quartiles of achieved HR at rest (p = 0.19 and p = 0.8, respectively) or achieved exercise HR (p = 0.77 and p = 0.14, respectively). After controlling for covariates, there remained no significant relation between either achieved HR at rest or achieved exercise HR and event-free survival (hazard ratio 0.95, p = 0.35 and hazard ratio 0.98, p = 0.81) or overall survival (hazard ratio 1.03, p = 0.70 and hazard ratio 1.22, p = 0.13). Furthermore, there was no significant association between achieved HR and QoL measurements, New York Heart Association functional class, or 6-minute walking distance. After 2 months of drug titration, neither achieved HR at rest nor achieved exercise HR predicted survival free from cardiovascular hospitalization, overall survival, QoL, or functional status among patients with AF.

Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

BACKGROUND: Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. This report describes the cause-specific modes of death in the AFFIRM treatment groups. METHODS AND RESULTS: All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee, and a mode of death was assigned. In AFFIRM, 2033 patients were randomized to a rhythm-control strategy and 2027 patients to a rate-control strategy. During a mean follow-up of 3.5 years, there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients (P=0.07). In the rhythm-control group, 129 patients (9%) died of a cardiac cause, and in the rate-control group, 130 patients (10%) died (P=0.95). Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths. The numbers of vascular deaths were similar in the 2 groups: 35 (3%) in the rhythm-control group and 37 (3%) in the rate-control group (P=0.82). There were no differences in the rates of ischemic stroke and central nervous system hemorrhage. In the rhythm-control group, there were 169 noncardiovascular deaths (47.5% of the total number of deaths), whereas in the rate-control arm, there were 113 noncardiovascular deaths (36.5% of the total number of deaths) (P=0.0008). Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths. CONCLUSIONS: Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate.

A computational model for the identification of biochemical pathways in the krebs cycle.

We have applied an algorithmic methodology which provably decomposes any complex network into a complete family of principal subcircuits to study the minimal circuits that describe the Krebs cycle. Every operational behavior that the network is capable of exhibiting can be represented by some combination of these principal subcircuits and this computational decomposition is linearly efficient. We have developed a computational model that can be applied to biochemical reaction systems which accurately renders pathways of such reactions via directed hypergraphs (Petri nets). We have applied the model to the citric acid cycle (Krebs cycle). The Krebs cycle, which oxidizes the acetyl group of acetyl CoA to CO(2) and reduces NAD and FAD to NADH and FADH(2), is a complex interacting set of nine subreaction networks. The Krebs cycle was selected because of its familiarity to the biological community and because it exhibits enough complexity to be interesting in order to introduce this novel analytic approach. This study validates the algorithmic methodology for the identification of significant biochemical signaling subcircuits, based solely upon the mathematical model and not upon prior biological knowledge. The utility of the algebraic-combinatorial model for identifying the complete set of biochemical subcircuits as a data set is demonstrated for this important metabolic process.