Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials.

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1-4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1-4 weeks benzodiazepines (SMD - 0.58, 95% CI - 0.77 to - 0.40), quetiapine (SMD - 0.51, 95% CI - 0.90 to - 0.13) and pregabalin (SMD - 0.58, 95% CI - 0.87 to - 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.

Definition of and delimitation of polyfarmaci.

At present, there is no clear and universal definition of polypharmacy. This review summarises the most common definitions and discusses the challenges in finding one suitable definition. Most of the literature has defined polypharmacy as the simultaneous use of five or more drugs. It is known that polypharmacy can lead to an increased risk of adverse health outcomes. However, a lot of medicine is not necessarily too much medicine. Preferentially, a definition should therefore differentiate between appropriate and inappropriate polypharmacy. As a universal definition has not yet been established, it is important to consider the definition used in the literature describing polypharmacy.

Involving frail older patients in identifying outcome measures for transitional care-a feasibility study.

BACKGROUND: During care transitions, the older (75+) patient's agenda can easily be missed. To counteract this, involving patients in shared clinical decision making has proven to be of great value. Likewise, involving patients and other stakeholders as researchers is gaining ground. Patient and public involvement (PPI) in research entails many benefits, for example, by bringing further insight from those with lived experiences of being ill. There are various challenges associated with involving some older patients, for example frailty, cognitive impairment and other chronic illnesses. To the best of our knowledge, there are only a few examples of initiatives involving older patients beyond research participation. The feasibility of involving frail older patients during an ongoing care transition from hospital to primary health care remains unknown. To investigate the feasibility of including older frail patients, their relatives and health care professionals (HCPs) as co-researchers, we established a study with increasingly demanding levels of patient involvement to identify relevant outcome measures for future transitional care research. METHODS: The study was a pragmatic, qualitative feasibility study. The involved individuals were frail older patients, their relatives and HCPs. Patients and their relatives were interviewed, while the interviewer made reflective notes. A thematic analysis was made. Relatives and HCPs discussed the themes to identify relevant outcome measures and potentially co-create new patient-reported outcome measures (PROMs) for use in future transitional care studies. The feasibility was evaluated according to six involvement steps. The level of involvement was evaluated using the five-levelled Health Canada Public Involvement Continuum (HCPIC). RESULTS: In total, eight patients, five relatives and three HCPs were involved in the study. Patients were involved in discussing care transitions (HCPIC level 3), while some relatives were engaged (HCPIC level 4) in forming PROMs. The partnership level of involvement (HCPIC level 5) was not reached. The thematic analysis and the subsequent theme discussion successfully formed PROMs. The key PROMs were related to care, transparency and the relatives' roles in the transitional care process. CONCLUSIONS: When applying a pragmatic involvement approach, frail older patients can be successfully involved in identifying relevant transitional care outcome measures; however, involving these patients as fellow researchers seems infeasible. To maintain involvement, supportive relatives are essential. Useful experiences for future research involvement of this vulnerable group were reported, arguing that patient participation has the potential to become inherent in future geriatric research.

The purpose of the study was to involve patients in identifying relevant outcome measures for future transitional care research. Involving patients in research is not new. What makes this project special is that it seeks to involve old, frail patients aged 75 plus.The project used open-form interviews that were not constrained in time and were not audio recorded; this was done to obtain confidence from the patients and their relatives. Each patient was interviewed twice: shortly before the patients left the hospital and shortly after discharge. The purpose was to discuss the patient's experiences during the discharge period. The first interview took place in the hospital, whereas the interviewer visited the patients in their residence for the second interview. An expert panel was then formed involving the patients' relatives and the professional health care workers. The expert panel discussed themes based on the data expressed by the patients during the interviews. In addition, an attempt was made to establish long-term cooperation between the patients, their relatives and the researchers. The health condition and vulnerable state of the patients made it difficult to continue their involvement throughout the research process. In fact, only the relatives and professionals were able to take part in the expert panel. Despite these challenges, the outcome of the project was positive. In conclusion, it makes sense to involve frail patients in transitional care research despite the challenges these patients face in their old age. In future research, frail older patients, relatives and other stakeholders can be involved.

Flow-induced [Ca2+]i increase depends on nucleotide release and subsequent purinergic signaling in the intact nephron.

Flow induces cytosolic Ca(2+) increases ([Ca(2+)](i)) in intact renal tubules, but the mechanism is elusive. Mechanical stimulation in general is known to promote release of nucleotides (ATP/UTP) and trigger auto- and paracrine activation of P2 receptors in renal epithelia. It was hypothesized that the flow-induced [Ca(2+)](i) response in the renal tubule involves mechanically stimulated nucleotide release. This study investigated (1) the expression of P2 receptors in mouse medullary thick ascending limb (mTAL) using P2Y(2) receptor knockout (KO) mice, (2) whether flow increases induce [Ca(2+)](i) elevations in mTAL, and (3) whether this flow response is affected in mice that are deplete of the main purinergic receptor. [Ca(2+)](i) was imaged in perfused mTAL with fura-2 or fluo-4. It is shown that luminal and basolateral P2Y(2) receptors are the main purinergic receptor in this segment. Moreover, the data suggest presence of basolateral P2X receptors. Increases of tubular flow were imposed by promptly rising the inflow pressure, which triggered a marked increase of [Ca(2+)](i). This [Ca(2+)](i) response was significantly reduced in P2Y(2) receptor KO tubules (fura-2 ratio increase WT 0.44 +/- 0.09 [n = 28] versus KO 0.16 +/- 0.04 [n = 13]). Furthermore, the flow response was greatly inhibited with luminal and basolateral scavenging of extracellular ATP (apyrase 7.5 U/ml) or blockage of P2 receptors (suramin 300 microM). The flow response could still be elicited in the absence of extracellular Ca(2+). These results strongly suggest that increase of tubular flow elevates [Ca(2+)](i) in intact renal epithelia. This flow response is caused by release of bilateral nucleotides and subsequent activation of P2 receptors.