Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

The Meaning of Social Support in Nature-Based Services for Young Adults with Mental Health Problems.

In previous studies, social context and social support have been found to be important in nature-based services. However, no studies have previously focused on the meaning of different dimensions of social support in these contexts. The aim of this study is therefore to uncover dimensions of social support in relation to mental health among young adults with mental health problems participating in nature-based services in Norway. This study applies data from a survey of 93 young adults participating in nature-based services; in addition, qualitative interview data from 20 interviews are also used. The data are analysed using qualitative content analysis, descriptive statistics, and correlation analysis. The results indicate that participants in nature-based services experience emotional, esteem, informational, and instrumental support in addition to social integration and opportunities for nurturance in these services. The service leader, other participants, and the animals are important contributors to these dimensions of social support. Nature-based services may be a helpful intervention for young adults with mental health problems. The unique context of these services, including nature and animals, adds special qualities to mental health and social work practices.

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain.

Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.

Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions.

PURPOSE: To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. METHODS: Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. RESULTS: Both regions examined, IR and UIR, exhibited over weeks 1-17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. CONCLUSION: This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture.

Route of Vaccine Administration Alters Antigen Trafficking but Not Innate or Adaptive Immunity.

Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization of targeted cells and tissues. Both s.c. and i.m. routes induce efficient immune cell infiltration, activation, and antigen uptake, functions that are tightly restricted to the skin and muscle, respectively. Antigen is also transported to different lymph nodes depending on route. However, these early differences do not translate into significant differences in the magnitude or quality of antigen-specific cellular and humoral responses over time. Thus, although some distinct immunological differences are noted, the choice of route may instead be motivated by clinical practicality.

Postoperative Thromboprophylaxis With New Oral Anticoagulants is Superior to LMWH in Hip Arthroplasty Surgery: Findings from the Swedish Registry.

BACKGROUND: Although the use of thromboprophylaxis is well established, there is no consensus on the preferred thromboprophylaxis regimen after THA; large, population-based studies offer an opportunity to examine this problem in a robust way that can complement results from randomized trials. QUESTIONS/PURPOSES: Using data from a large national registry, we asked: (1) Is there any difference between low-molecular weight heparin (LMWH) and new oral anticoagulants in preventing symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), after THA? (2) Are there any differences in safety parameters, such as bleeding, reoperations and mortality, between LMWH and new oral anticoagulants? METHODS: Between 2008 and 2012, 78,066 THAs were performed in Sweden. This study evaluated 32,663 (42%) of them, selected through the merger of several national registries. These patients underwent unilateral THA due to primary osteoarthritis. They had not experienced any venous thromboembolic events 5 years before the index operation and were not prescribed potent antithrombotic agents, of any type, in the 6 months before the index operation. Additionally, their postoperative thromboprophylaxis was confirmed in a national registry by purchase of prescribed medications. We divided the cohort into two groups: those patients who received new oral anticoagulants (5752, 18%) and those who received LMWH (26,881, 82%) as postoperative thromboprophylaxis. Our primary endpoints were the frequencies of symptomatic DVT and symptomatic PE within 3 months of surgery. Our secondary comparison was a between-group comparison of bleeding (by way of diagnostic coding), reoperation, and mortality within 3 months of surgery. Odds ratios (OR) are presented with 95% confidence intervals (CIs) as pooled results for the two groups after adjustment for duration of thromboprophylaxis (short or extended for at least 28 days), year of the index operation, Elixhauser comorbidity index, sex, age and previous treatment with platelet aggregation inhibitors. RESULTS: The risk of symptomatic DVT was lower in the group that received new oral anticoagulants than the group that received LMWH (0.3% versus 0.6%, OR, 0.47; 95% CI, 0.27-0.76; p = 0.026). The risk of symptomatic PE was lower in the group that received new oral anticoagulants than the group that received LMWH (0.1% versus 0.4%, OR, 0.36; 95% CI, 0.16-0.69; p = 0.005). There was no difference in the risk of bleeding (by way of diagnostic coding) (OR, 1.03; 95% CI, 0.82-1.28; p = 0.688), reoperation (OR, 1.02; 95% CI, 0.71-1.44; p = 0.860) or mortality (OR, 0.83; 95% CI, 0.31-1.88; p = 0.883) between groups. CONCLUSIONS: New oral anticoagulants were associated with a lower risk of symptomatic DVT and symptomatic PE in this large, registry study, and we observed no differences in the risk of bleeding, reoperation, or death between the groups. Although we were able to control for a number of potential confounding variables, we cannot ascertain the indications that drove the prescription decisions in this setting, and there were important between-group differences in terms of duration of thromboprophylaxis (new oral anticoagulants generally were used for a longer period of time after surgery). Future studies, preferably large randomized trials with pragmatic inclusion criteria, to analyze symptomatic DVT, symptomatic PE and death are needed to confirm or refute our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

[The role of NOAC in orthopaedic surgery - pros and cons]. / NOAK som trombosprofylax vid ortopedisk kirurgi - Ger både fördelar och nackdelar ­ randomiserade studier saknas ännu om hur NOAK ska hanteras vid kirurgi.

The risk for venous thromboembolism (VTE) is high in orthopaedic surgery in the lower extremities and pelvis. New oral anticoagulants (NOAC) have been shown to be efficient and safe as thrombosis prophylaxis after hip and knee arthroplasty surgery. The increased use of NOAC as prophylaxis in atrial fibrillation patients causes new problems in acute and elective surgery.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-ß have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition.

An open-label study of the pharmacokinetics and pharmacodynamics of dabigatran etexilate 150mg once daily in Caucasian patients with moderate renal impairment undergoing primary unilateral elective total knee or hip replacement surgery.

BACKGROUND: In adults with moderate renal impairment (creatinine clearance [CrCl] 30-50mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. METHODS: Single-arm, open-label phase 4 study (NCT01184989) in Caucasian patients receiving dabigatran etexilate 75mg 1-4h after surgery and 150mg qd on days 2-10 (TKR) or days 2-35 (THR). Plasma total dabigatran concentrations (day 6±1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot® Thrombin Inhibitors). RESULTS: Of 112 patients (mean CrCl 42.5mL/min, age 79.1years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5ng/mL (10th-90th percentile 19.7-120) and 166ng/mL (49.1-364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50-500ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of ±15%. CONCLUSIONS: These findings in Caucasians with moderate renal impairment undergoing THR or TKR support the use of the 150mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful.

Parkinsonism as a side effect of infliximab.

We present a case of a 64-year-old man with Crohn's disease who developed parkinsonism after starting treatment with infliximab (Remicade). The patient had a 30-year history of Crohn's disease with previous surgical procedures and treatment with methotrexate. Treatment was augmented with infliximab, and 3 days after the first dose of 400 mg, a resting tremor began in the left leg. Over 4 months, symptoms progressed and now involved the right leg as well as both hands. There was no clinical effect of infliximab treatment, and the treatment was withdrawn 4 months later. The patient then experienced gradual, but continual, improvement of the resting tremor after withdrawal of infliximab. To the best of our knowledge, this is the first case report describing a patient developing parkinsonism after starting treatment with infliximab, with symptoms remitting on discontinuation.

Preoperative plasma fibrinogen concentration, factor XIII activity, perioperative bleeding, and transfusions in elective orthopaedic surgery: A prospective observational study.

BACKGROUND: Major orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. METHODS: Two hundred and forty-five adult patients undergoing spine fusion surgery (n=52), total unilateral primary hip arthroplasty (n=114), or total knee arthroplasty (n=79) were included in a prospective observational study. Blood samples were collected <24h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. RESULTS: Spinal fusion surgery patients with a low preoperative fibrinogen concentration (≤2.5g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen>2.5g/L (2430 (400-6560) mL vs. 1390 (400-7420) mL, p=0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. CONCLUSION: Measurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding.

Sex Differences in Outcome After an Acute Achilles Tendon Rupture.

BACKGROUND: Tendon healing differs between the sexes. Comparisons in outcome between the sexes after an Achilles tendon rupture are often not possible because of the small cohort (<20%) of women. PURPOSE: To evaluate whether there are any differences in outcome between the sexes by combining the data from 2 large randomized controlled trials that used identical outcome measures. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included in the evaluation were patients from 2 consecutive randomized controlled trials comparing surgical and nonsurgical treatment performed at our research laboratory. Patients who had a rerupture were excluded from analysis. A total of 182 patients (152 males, 30 females), with mean ± SD age of 40 ± 11 years, were included; 94 (76 males, 18 females) were treated with surgery and 88 (76 males, 12 females) nonsurgically. Patient-reported outcome was evaluated using the Achilles tendon Total Rupture Score (ATRS), and the functional outcome was measured with a heel-rise test (measurement of muscular endurance and heel-rise height) at 6 and 12 months after injury. RESULTS: Male patients had a greater improvement in heel-rise height at 12 months (P = .004). When each treatment group was analyzed separately, it was found that female patients had significantly (P < .03) more symptoms after surgical treatment (mean ± SD ATRS, 59 ± 24) compared with males at 6 (73 ± 19) and 12 months (74 ± 27 vs 86.5 ± 17). This sex difference was not found in the nonsurgical treatment group. For the entire group, there were no significant differences between treatments on ATRS at 6 and 12 months. The surgical group had significantly better results compared with the nonsurgical group in heel-rise endurance at 6 and 12 months and in heel-rise height recovery at 6 months (P < .03 for both). CONCLUSION: Sex differences were demonstrated, and female patients had a greater degree of deficit in heel-rise height as compared with males, irrespective of treatment. Females had more symptoms after surgery both at 6 and 12 months, but this difference was not found when treated nonsurgically. CLINICAL RELEVANCE: Further research is needed to determine whether women will benefit more from nonsurgical compared with surgical treatment after an Achilles tendon rupture.

Hand Contamination, Cross-Transmission, and Risk-Associated Behaviors: An Observational Study of Team Members in ORs.

Team members in ORs have frequent hand contact with many surfaces and sites during high workload, thus increasing the risk for microorganism cross-transmission. This study aimed at identifying risks for hand contamination and microorganism cross-transmission during invasive procedures in ORs. We carried out observations during 22 daytime sessions and analyzed data using qualitative content analysis. The results revealed that clinicians' hands may be contaminated by self-contamination, via objects, or by touching the patient. Contamination may occur before, during, or directly after performing an invasive procedure requiring the use of aseptic technique, which risks cross-transmitting microorganisms. The results of the study contribute detailed knowledge about risk-associated activities and behaviors in relation to performing invasive procedures in the OR. This knowledge provides clinicians, managers, and educators with specific information that can be used in nursing and medical education and in quality improvement projects aimed at improving hand hygiene routines and enhancing aseptic technique.

Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials.

BACKGROUND: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. METHODS: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. RESULTS: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. CONCLUSIONS: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. TRIAL REGISTRATION: NCT00657150 and NCT00168818.

Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing.

BACKGROUND: The recent discovery of residing tendon stem/progenitor cells has triggered a growing interest in stem cells as a useful tool in tendon repair. Our knowledge of their involvement in naturally healing tendons is, however, sparse. The aim of this study was to identify and determine stem/progenitor cells in relation to different healing phases and regions in a rat model of Achilles tendon rupture. METHODS: Surgery was performed to create a mid-tendon rupture on the right Achilles tendon of 24 rats, whereas the left tendon was used as a control. Tendons were harvested at one, two, eight and 17 weeks post-rupture and stained with antibodies specific to stem/progenitor cells (Octamer-binding transcription factor 3/4 (Oct 3/4) and nucleostemin), migrating cells (Dynamin 2 (Dyn 2)) and leukocytes (CD45). A histological examination was performed on sections stained with Alcian blue. RESULTS: At one and two weeks post-rupture, a large number of stem/progenitor cells were discovered throughout the tendon. Most of these cells were nucleostemin positive, whereas only a few Oct 3/4-positive cells were found, mainly situated inside the injury region (I region). At eight and 17 weeks, the increment in stem/progenitor cells had diminished to equal that in the control tendons. At all time points, Oct 3/4-positive cells were also found in the connective tissue surrounding the tendon and at the muscle-tendon junction in both ruptured and control tendons and were often seen at the same location as the migration marker, Dyn 2. CONCLUSIONS: The whole length of the Achilles tendon is infiltrated by stem/progenitor cells at early time points after a mid-tendon rupture. However, different stem/progenitor cell populations exhibit varying anatomical and temporal expressions during Achilles tendon healing, suggesting distinct reparative implications. Oct 3/4 may thus act as a more local, migrating stem/progenitor cell involved in injury-site-specific regenerative effects, as compared to the more general proliferative role of nucleostemin-positive stem/progenitor cells.

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

BACKGROUND: There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. METHODS/MATERIALS: In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. RESULTS: Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. CONCLUSIONS: The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Hand hygiene and aseptic techniques during routine anesthetic care - observations in the operating room.

BACKGROUND: More knowledge is needed about task intensity in relation to hand hygiene in the operating room during anesthetic care in order to choose effective improvement strategies. The aim of this study was to explore the indications and occurrence of hand hygiene opportunities and the adherence to hand hygiene guidelines during routine anesthetic care in the operating room. METHODS: Structured observational data on hand hygiene during anesthetic care during 94 surgical procedures was collected using the World Health Organization's observational tool in a surgical department consisting of 16 operating rooms serving different surgical specialties such as orthopedic, gynecological, urological and general surgery. RESULTS: A total of 2,393 opportunities for hand hygiene was recorded. The number of hand hygiene opportunities when measured during full-length surgeries was mean = 10.9/hour, SD 6.1 with an overall adherence of 8.1%. The corresponding numbers for the induction phase were, mean =77.5/h, SD 27.4 with an associated 3.1% adherence to hand hygiene guidelines. Lowest adherence was observed during the induction phase before an aseptic task (2.2%) and highest during full-length surgeries after body fluid exposure (15.9%). CONCLUSIONS: There is compelling evidence for low adherence to hand hygiene guidelines in the operating room and thus an urgent need for effective improvement strategies. The conclusion of this study is that any such strategy should include education and practical training in terms of how to carry out hand hygiene and aseptic techniques and how to use gloves correctly. Moreover it appears to be essential to optimize the work processes in order to reduce the number of avoidable hand hygiene opportunities thereby enhancing the possibilities for adequate use of HH during anesthetic care.

Mental health nurses responding to suffering in the 21st century occidental world: accompanying people in their search for meaning.

Much of contemporary health and mental health practice pays little attention to suffering, and when it does, invariably suffering is conflated with pain. Within such views, the health care practitioner ought to be concerned with removing or stopping the suffering as, for many parts of the occidental world at least, suffering is regarded as antagonistic to the pursuit of happiness. However, it has been recognized since ancient times that the experience of suffering can give rise to growth. This view sees suffering as an inevitable aspect of the human condition and experience; as something that might need to be endured, minimized, relieved, explored for meaning and maybe even learned from. The former conceptualization of suffering leaves little, if any, room for the sufferer to be to be proud of his suffering and to consider it ennobling rather than degrading, and such views are highly congruent with the increased pathologizing of 'everyday life' and with that, the inexorable proliferation of pharmacological 'treatment'. Accordingly, we assert that there is a clear need for Psychiatric/Mental Health nurses to re-think their views of suffering and consider how they might help the person discover meaning in the experience; how they might accompany the individual on his/her suffering journey. We therefore identify a range of approaches and interventions that Psychiatric/Mental Health nurses can use when attempting to help those experiencing mental health-related suffering.