A Nationwide Mystery Caller Evaluation of Oral Emergency Contraception Practices from German Community Pharmacies: An Observational Study Protocol.

To prevent unwanted pregnancies, oral emergency contraception (EC) with the active ingredients levonorgestrel (LNG) and ulipristal acetate (UPA) is recommended by the guidelines of the German Federal Chamber of Pharmacists (BAK). In this respect, community pharmacies (CPs) in Germany have a major responsibility for information gathering, selecting the appropriate medicine, availability and pricing, among other things. Therefore, it would be appropriate to conduct a study with the aim of investigating information gathering, a possible recommendation as well as availability and pricing for oral EC in German CPs. A representative nationwide observational study based on the simulated patient methodology (SPM) in the form of covert mystery calls will be conducted in a random sample of German CPs stratified according to the 16 federal states. Each selected CP will be randomly called once successfully by one of six both female and male trained mystery callers (MCs). The MCs will simulate a product-based scenario using the request for oral EC. For quality assurance of the data collection, a second observer accompanying the MC is planned. After all mystery calls have been made, each CP will receive written, pharmacy-specific performance feedback. The only national SPM study on oral EC to date has identified deficits in the provision of self-medication consultations with the help of visits in the CPs studied. International studies suggest that UPA in particular is not always available. Significant price differences could be found analogous to another German study for a different indication.

Vagal and Sympathetic Function in Neuropathic Postural Tachycardia Syndrome.

The diagnosis of neuropathic postural tachycardia syndrome (POTS) requires research techniques not available clinically. We hypothesized that these patients will have impaired vagal and sympathetic cardiovascular control that can be characterized with clinical autonomic tests. We included 12 POTS patients with possible neuropathic subtype because of normal plasma norepinephrine and no increase in upright blood pressure. We compared them to 10 healthy subjects. We assessed hemodynamics, heart rate and blood pressure variability, baroreflex sensitivity, raw and integrated muscle sympathetic nerve activity, and blood volume. To understand the vagal/sympathetic control, we dissected the phase 2 of Valsalva maneuver (VM) into early (VM2e) and late (VM2l). POTS' upright heart rate increased 43±3 bpm. Patients had normal plasma volume but reduced red blood cell volume (1.29 L versus predicted normal values 1.58 L; P=0.02). Vagal indices of heart rate variability, HFRRI (430±130 versus 1680±900; P=0.04), PNN50, and root mean squared of successive differences were lower in POTS. Patients showed a decrease in vagal baroreflex sensitivity (VM2e; P=0.04). In POTS, integrated muscle sympathetic nerve activity was lower at rest (12±1.5 versus 20±2 burst/min; P=0.004) and raw muscle sympathetic nerve activity spike analysis showed blunted responses during VM2e, despite a greater drop in systolic blood pressure (34±5 in POTS and 14±6 mm Hg in controls; P=0.01). This cohort of POTS patients enriched for possible neuropathic subtype had lower resting muscle sympathetic nerve activity, impaired vagal cardiac control, and exaggerated drop in blood pressure in response to VM and a delay in the sympathetic cardiovascular responsiveness during hypotensive challenge.

Hell is other people? Gender and interactions with strangers in the workplace influence a person's risk of depression.

We suggest that interactions with strangers at work influence the likelihood of depressive disorders, as they serve as an environmental stressor, which are a necessary condition for the onset of depression according to diathesis-stress models of depression. We examined a large dataset (N = 76,563 in K = 196 occupations) from the German pension insurance program and the Occupational Information Network dataset on occupational characteristics. We used a multilevel framework with individuals and occupations as levels of analysis. We found that occupational environments influence employees' risks of depression. In line with the quotation that 'hell is other people' frequent conflictual contacts were related to greater likelihoods of depression in both males and females (OR = 1.14, p<.05). However, interactions with the public were related to greater likelihoods of depression for males but lower likelihoods of depression for females (ORintercation = 1.21, p<.01). We theorize that some occupations may involve interpersonal experiences with negative emotional tones that make functional coping difficult and increase the risk of depression. In other occupations, these experiences have neutral tones and allow for functional coping strategies. Functional strategies are more often found in women than in men.

Lateralization of expression of neural sympathetic activity to the vessels and effects of carotid baroreceptor stimulation.

Human studies suggest that cardiovascular neural sympathetic control is predominantly modulated by the right cerebral hemisphere. It is unknown whether post-ganglionic sympathetic activity [muscle sympathetic nerve activity (MSNA)] shows any functional asymmetry. Eight right-handed volunteers (3 women and 5 men, 32 +/- 2 yr of age) underwent ECG, beat-by-beat blood pressure, respiratory activity, and simultaneous right and left MSNA recordings during spontaneous and controlled breathing (CB, 15 breaths/min, 0.25 Hz). Dynamic carotid baroreceptor stimulation was obtained by 0.1-Hz sinusoidal suction, from 0 to -50 mmHg, randomly applied to the right, left, and combined right and left sides of the neck during CB. Laterality was assessed by changes in the MSNA burst rate (in bursts/min, and bursts/100 beats), strength [amplitude (A) and area (AA)], and the oscillatory component at 0.1 Hz during baroreceptor stimulation. Amplitude parameters were normalized by CB burst mean amplitude and area of the same side. At rest, the right and left MSNA burst rate and total MSNA activity were similar. Conversely, the right MSNA normalized burst A(N) (1.36 +/- 0.18) and AA(N) (1.31 +/- 0.16) were larger than the left MSNA A(N) (1.04 +/- 0.09) and AA(N) (1.02 +/- 0.08). Unilateral and bilateral carotid baroreflex stimulation abolished the right prevalence of A(N) and AA(N). In conclusion, the right lateralization of sympathetic activity to the vessels is indicated by normalized burst strength parameters of bilateral MSNA recordings at rest during spontaneous breathing. Carotid baroreceptor stimulation disrupted such expression of MSNA lateralization possibly by disturbing the synchronizing action of right cerebral hemisphere.

The impact of blood pressure and baroreflex sensitivity on wind-up.

BACKGROUND: Elevated resting blood pressure (BP) and spontaneous baroreflex sensitivity (BRS) are associated with hypoalgesia to acute pain. These associations are significantly altered in chronic pain. We investigated whether degree of wind-up (marker for central sensitization) is similarly influenced by BP and BRS, and whether these associations are altered by chronic pain. METHODS: BP and BRS (sequence method) were assessed in 30 healthy and 26 chronic back pain subjects who then completed a standardized thermal stimulation protocol to assess wind-up. This protocol was performed under placebo and alpha-2 adrenergic (ADRA2) blockade with yohimbine in counterbalanced order to test for the influence of ADRA2 mechanisms. RESULTS: 1) In healthy controls, higher systolic BP was associated with lower wind-up (P < 0.05) but this was reversed in chronic pain subjects (P < 0.05); 2) higher BRS was associated with lower wind-up in healthy controls (P < 0.05) but not in the chronic pain group; 3) higher systolic BP was associated with lower BRS only in the chronic pain group (P < 0.05); and 4) ADRA2 receptor blockade did not significantly affect wind-up. CONCLUSIONS: These findings suggest that hypoalgesia associated with elevated resting BP and BRS in healthy individuals involves both diminished central sensitization (reflected in wind-up) and enhanced descending inhibition. The presence of chronic pain significantly alters the nature of these interactions. The reversal of normal interactions between overlapping systems modulating cardiovascular systems and pain in chronic pain patients may shift the healthy buffering of BP and heart rate toward instability and eventual higher BP and cardiovascular morbidity.

Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain.

While experimental baroreceptor stimulation is known to elicit hypoalgesia in healthy individuals, the impact of spontaneous baroreflex sensitivity (BRS) on acute pain responses is not known. We tested for associations between BRS and pain responses in healthy individuals, whether these associations are altered in chronic low back pain (CLBP), and the role of alpha-2 adrenergic (ADRA2) mechanisms in these effects. Twenty-five healthy controls and 21 CLBP subjects completed three acute pain tasks after receiving placebo or an intravenous ADRA2 antagonist (yohimbine hydrochloride, 0.4 mg/kg) across two sessions in counterbalanced order. Resting pre-drug spontaneous BRS was assessed using the sequence method. CLBP subjects displayed lower resting BRS(Down) than controls (p<.05). Drug x BRS(Down) interactions indicated that significant BRS-related hypoalgesia on thermal pain threshold and tolerance was eliminated with yohimbine (p's<.05). Subject Type x BRS(Up) interactions on finger pressure (MPQ-Sensory) and ischemic tasks (MPQ-Sensory, pain threshold, intra-task numeric intensity ratings) indicated that inverse BRS/pain associations in controls (p's<.05) were absent in CLBP subjects. Subject TypexDrug x BRS(Down) interactions on finger pressure MPQ-Sensory and intra-task numeric intensity ratings (p's<.05) indicated that for controls, yohimbine attenuated the significant inverse BRS/pain sensitivity associations noted under placebo. In contrast, CLBP subjects displayed a nonsignificant positive BRS/pain association under placebo, with yohimbine producing an inverse association similar to controls (significant for MPQ-Sensory). Results suggest presence of spontaneous BRS-related hypoalgesia in healthy individuals that is partially mediated by ADRA2 mechanisms, and that CLBP blunts BRS-related hypoalgesia. As a group, the CLBP subjects do not manifest baroreceptor-induced antinociception.

The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade.

This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure x Participant Type x Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug x Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type x Systolic Blood Pressure interactions (P's < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.

Trait anger expressiveness and pain-induced beta-endorphin release: support for the opioid dysfunction hypothesis.

The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness. Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction. The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids. Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p's<.05). Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced BE increases (p<.05). Subject type did not moderate this association (p>.10). Anger-in did not display significant main or interaction effects on pain-induced BE changes (p's>.10). The significant association between anger-out and BE release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect. This suggests unique associations with expressive anger regulation. Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels. Possible "statextrait" interactions on these anger-related opioid system differences are discussed.

Effects of unilateral and bilateral carotid baroreflex stimulation on cardiac and neural sympathetic discharge oscillatory patterns.

BACKGROUND: Left and right carotid baroreflex afferents participate in generating the spontaneous variability of heart rate (HR), arterial pressure (AP), and muscle sympathetic nerve activity (MSNA), but the relative contribution of each side is unclear. Pathophysiological conditions unilaterally affecting carotid baroreceptor function might result in abnormal changes of HR, AP, and MSNA variability, thus markedly affecting prognosis. We tested the hypothesis that unilateral carotid baroreceptor perturbation might differentially affect HR, AP, and MSNA variability compared with stimulation of the opposite side. METHODS AND RESULTS: In 12 healthy volunteers, 4 sinusoidal neck suction procedures (0.1 Hz, from 0 to -50 mm Hg) were applied at the right, left, and combined right and left sides of the neck, in concordance or with phase opposition. Respiration was controlled at 0.25 Hz. Power spectrum analysis assessed the changes in the 0.1-Hz oscillatory component of the R-R interval, systolic AP (SAP), and MSNA variability induced by rhythmic baroreceptor stimulation. Mean R-R interval, SAP, and MSNA were unchanged during all procedures. The increase of the 0.1-Hz component of R-R and SAP variability during right and combined right and left carotid baroreceptor stimulation was greater than the changes induced by left-sided stimulation. The increase in the 0.1-Hz oscillatory component of MSNA variability was similar during all neck suction procedures. CONCLUSIONS: Right carotid baroreflex loading was as efficient as bilateral stimulation and more effective than left carotid suction in modulating R-R and SAP variability. There was no asymmetry in neural sympathetic discharge responses after single-sided carotid baroreceptor stimulation.

Hypoglycemia associated autonomic failure.

Intensively treated patients with diabetes have a three-fold increased risk of severe hypoglycemic episodes with an attendant four percent mortality. These findings, unfortunately undermine attempts to achieve normoglycemia in diabetic patients. It has been proven that antecedent hypoglycemia is a major factor responsible for blunting metabolic, neuroendocrine and also autonomic responses to subsequent hypoglycemia. Diabetic patients with good glycemic control become unable to recognize symptoms of hypoglycemia. Lack of symptoms, or hypoglycemia unawareness, is part of the syndrome called hypoglycemia associated autonomic failure. This syndrome also includes inadequate neuroendocrine hormonal responses and reduced glycemic thresholds for counterregulatory hormonal secretion. Factors regulating the magnitude of hypoglycemia associated autonomic failure include antecedent duration and frequency of hypoglycemia, prior episodes of exercise, and autonomic neuropathy. Understanding the pathophysiology of this syndrome will provide a foundation for therapy aimed at preventing severe hypoglycemia during intensive metabolic control. This article will review our current understanding of the mechanisms responsible for hypoglycemia associated autonomic failure.