Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017

Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

Kinesio Taping vs. Auricular Acupressure for the Personalised Treatment of Primary Dysmenorrhoea: A Pilot Randomized Controlled Trial

Background: Dysmenorrhoea is the medical term for menstrual pain. The World Health Organization estimates that up to 81% of women of childbearing age are affected by this condition, and it is one of the leading causes of absenteeism from work and school among women. Although there are pharmacological treatments available for menstrual-pain relief, they do not respond to all women’s needs. Therefore, there is a need to study and develop non-pharmacological alternatives to broaden the individualised treatment options for dysmenorrhea. There are scarce studies published on non-pharmacological treatments, such as kinesio tape and auricular acupressure for the relief of menstrual pain, but the scientific evidence available suggest that these techniques may be beneficial in addressing this problem. The objective of this pilot study was to assess and compare the effectiveness of kinesio tape and auricular acupressure to decrease pain and drug intake in women with primary dysmenorrhoea. Methods: This was a double-blind randomized clinical controlled trial. The period of study was from September 2017 to August 2018. Women enrolled in the University of Extremadura and who had primary dysmenorrhoea were randomized to five groups: control (n = 23), kinesio tape (n = 23), placebo kinesio tape (n = 23), auricular acupressure (n = 23) and placebo auricular acupressure (n = 22). Measures were taken during the pretreatment phase (at four menstrual cycles), during the post-intervention phase (at four menstrual cycles) and during the follow-up phase (at the first and third menstrual cycles after the treatment was completed). The primary outcome measures were mean pain intensity, maximum pain intensity, number of painful days and dose of drug intake during menstruation, measured with the Visual Analogue Scale. The secondary outcome measures were the length of the cycle, the length of menstruation, the drug intake and the type of drug. Results: In all, 108 participants completed the study. The statistical analysis (MANOVA, ANOVA, t-paired and McNemar tests) showed that kinesio tape and auricular acupressure have a beneficial effect on pain relief (mean pain intensity, p < 0.001; maximum pain intensity, p < 0.001; number of painful days, p = 0.021; dose of drug intake, p < 0.001). In addition, once the treatments were withdrawn, the auricular-acupressure group maintained lower scores during the first follow-up cycle (p < 0.001). Conclusions: Kinesio tape and auricular acupressure decrease pain and drug intake in women with primary dysmenorrhoea. The changes in the auricular-acupressure group seemed to last longer. The results suggest that these techniques could be used as complementary personalised therapies to the pharmacological treatment and not as a substitution.

Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence

Patients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence.

Pillbox: Medicine Recognition System for Chronic Patients using Raspberry Pi

Chronic disease has become important threat to be handled in today’s date. As per WHO the millions of people suffering from this disease and most of them are older ones. Overall death rate in country is effecting due to chronic disease. The main reason of increased number of chronic patients is nothing but having lot of medications because of having number of health conditions as well as increased percentage of drugs in patient’s body. So, the system introduced successfully works to reduce death rate as well as to minimize drug intake in patient’s body. The system comprises of raspberry pi based pill recognition device namely “Pillbox”, Apache cloud based platform and android based mobile application.

PROBLEMS OF SIDE EFFECT OF USE OF THE MEDICINES OFF LABEL

Drugs which as we hope, have to facilitate or save the patient's life sometimes cause the return ˗ the collateral reactions (CR) and even death. CR of drugs can be a cause of death not less, than sepsis and accidents. Often the wrong dispensing and also the medicines prescribed by off label is their reason (out of the instruction). The aim of the study. To analyze the frequency of manifestation of collateral reactions of medicines at their application of off label. Materials and methods. The analysis of foreign and domestic scientific publications concerning manifestation of collateral reactions of drugs at their application off label. Results. Today there are no concrete data on that how many deadly CR happen because of off label of drugs, but it is possible to estimate it, using information which is known: CR at drug intake of off label occur approximately by two-three times more often than at drug intake of on label (according to the instruction). It is established that lower or higher dose of medicine, than that which is specified in the instruction can lead to security concerns. Use of off label of medicines in doses is higher than those which were approved by the instruction, correlate with increase in risk of development of CR. It is established that prescription of medicines of off label is connected with higher risk of CR, than with their licensed alternatives, and hypotheses in literature concerning efficiency and harmlessness of off label of use of drugs not always are reliable. Conclusions. The doctor and the pharmacist need to remember that positive effects of application of off label of drugs have to have synergism with their safety that the medicine off label, very necessary for the patient, did not appear without the obligatory quality ˗ safety.

Peer presence and familiarity as key factors to reduce cocaine intake: an effect mediated by the Subthalamic Nucleus

Stimulant use, including cocaine, often occurs in a social context whose influence is important to understand to decrease intake and reduce associated harms. Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigate its role on such influence of social context on cocaine intake. We explored the influence of peer presence and familiarity on the frequency of self-administered cocaine and its neurobiological basis. We first compared cocaine intake in various conditions (alone or with peers with different characteristics: observing or self-administering, familiar or not, cocaine-naive or not, dominant or subordinate) in rats (n=90). The risk of drug consumption was reduced when a peer was present, observing or self-administering as well, and further diminished when the peer was unfamiliar (vs familiar). The presence of a cocaine-naive peer further decreased cocaine consumption. The presence of a non-familiar and drug-naive peer represents thus key conditions to diminish cocaine intake. We tested the effects of STN lesions in these various conditions and also conducted social experiments to validate the role of STN in social cognition. The STN lesion by itself reduced cocaine intake to the level reached in presence of a stranger naive peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drug intake. Finally, with a translational research approach, we compared the drug intake in these conditions in human drug users (n=77). This human study confirmed the beneficial effect of social presence, especially of strangers. Our results indirectly support the use of social interventions and harm reduction strategies, in particular supervised consumption rooms for stimulant users.

Management of ongoing direct anticoagulant treatment in patients with hip fracture

Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p < 0.0001) and treatment within 48 h was 47% vs. 80% in control group (p < 0.0001). The adherence to guidelines’ suggested time from last drug intake to surgery was 46%. Neither anticipation nor delay in surgery did result in increased mortality, length of stay or complication rates with the exception of larger perioperative blood loss (Hb levels < 8 g/dl) in DOACs patients (34% vs 9% p < 0.0001). Present results suggest that time to surgery is significantly longer in DOAC patients in comparison to controls and adherence to guidelines still limited.