Engineering Crystals Using sp3 -C Centred Tetrel Bonding Interactions.

1,1,2,2-Tetracyanocyclopropane derivatives 1 and 2 were designed and synthesized to probe the utility of sp3 -C centred tetrel bonding interactions in crystal engineering. The crystal packing of 1 and 2 and their 1,4-dioxane cocrystals is dominated by sp3 -C(CN)2 ⋅⋅⋅O interactions, has significant C⋅⋅⋅O van der Waals overlap (≤0.266 Å) and DFT calculations indicate interaction energies of up to -11.0 kcal mol-1 . A cocrystal of 2 with 1,4-thioxane reveals that the cyclopropane synthon prefers interacting with O over S. Computational analyses revealed that the electropositive C2 (CN)4 pocket in 1 and 2 can be seen as a strongly directional 'tetrel-bond donor', similar to halogen bond or hydrogen bond donors. This disclosure is expected to have implications for the utility of such 'tetrel bond donors' in molecular disciplines such as crystal engineering, supramolecular chemistry, molecular recognition and medicinal chemistry.

Observations of tetrel bonding between sp3-carbon and THF.

We report the direct observation of tetrel bonding interactions between sp3-carbons of the supramolecular synthon 3,3-dimethyl-tetracyanocyclopropane (1) and tetrahydrofuran in the gas and crystalline phase. The intermolecular contact is established via σ-holes and is driven mainly by electrostatic forces. The complex manifests distinct binding geometries when captured in the crystalline phase and in the gas phase. We elucidate these binding trends using complementary gas phase quantum chemical calculations and find a total binding energy of -11.2 kcal mol-1 for the adduct. Our observations pave the way for novel strategies to engineer sp3-C centred non-covalent bonding schemes for supramolecular chemistry.

Advance Care Planning in Frail Older Adults: A Cluster Randomized Controlled Trial.

OBJECTIVES: To determine the effectiveness of advance care planning (ACP) in frail older adults. DESIGN: Cluster randomized controlled trial. SETTING: Residential care homes in the Netherlands (N=16). PARTICIPANTS: Care home residents and community-dwelling adults receiving home care (N=201; n=101 intervention; n=100 control). Participants were 75 years and older, frail, and capable of consenting to participation. INTERVENTION: Adjusted Respecting Choices ACP program. MEASUREMENTS: The primary outcome was change in patient activation (Patient Activation Measure, PAM-13) between baseline and 12-month follow-up. Secondary outcomes included change in quality of life (SF-12), advance directive (AD) completion, and surrogate decision-maker appointment. Use of medical care in the 12 months after inclusion was also assessed. Multilevel analyses were performed, controlling for clustering effects and differences in demographics. RESULTS: Seventy-seven intervention participants and 83 controls completed the follow-up assessment. There were no statistically significant differences between the intervention (-0.26±11.2) and control group (-1.43±10.6) in change scores of the PAM (p=.43) or the SF-12. Of intervention group participants, 93% completed an AD, and 94% appointed a decision-maker. Of control participants, 34% completed an AD, and 67% appointed a decision-maker (p<.001). No differences in the use of medical care were found. CONCLUSIONS: ACP did not increase levels of patient activation or quality of life but did increase completion of ADs and appointment of surrogate decision-makers. It did not affect use of medical care.

Low patient activation levels in frail older adults: a cross-sectional study.

BACKGROUND: Frail older adults are increasingly expected to self-manage their health and healthcare. We assessed the extent to which this group is able to take up this responsibility by measuring their level of activation as patients (i.e. their knowledge, skills and confidence to self-manage their health and healthcare). Further, we studied which characteristics of older adults were associated with patient activation. METHODS: In this cross-sectional study 200 frail, competent adults (median age 87 years) participated. Participants were community-dwelling adults who received home care and residents of care homes. Data were collected via personal interviews in participants' homes. The main outcome measure was patient activation assessed by the short version of the Patient Activation Measure (PAM-13; range: 0-100). The PAM distinguishes four levels of increasing activation with level 1 indicating poor patient activation and level 4 adequate patient activation. Other studied variables were: multimorbidity, type of residency, frailty (Tilburg Frailty Index), mental competence (Mini Mental State Examination), health-related quality of life (SF-12), satisfaction with healthcare (subscale Patient Satisfaction Questionnaire) and personal characteristics (age, gender, marital status, educational level). Regression analyses were performed to investigate which variables were associated with patient activation. RESULTS: Participants had a median PAM score of 51. Thirty-nine percent had level 1 activation, 31% level 2, 26% level 3 and 5% level 4. Fifty-nine percent of community dwelling adults had level 1 or 2 activation versus 81% of care home residents (p = 0.007). Mental competence (Effect: 0.52, CI: 0.03-1.01, p = 0.04) and health-related quality of life (Effect: 0.15, CI: 0.01-0.30, p = 0.04 for physical health; Effect: 0.20, CI: 0.07-0.34, p = 0.003 for mental health) were positively associated with patient activation. Frailty (Effect: -1.06, CI: -1.75 - -0.36, p = 0.003) was negatively associated with patient activation. CONCLUSIONS: The majority of this frail and very old study population, especially those with a lower health-related quality of life, may be unable to self-manage their health and healthcare to the level expected from them. The increasing population of frail older adults may need help in managing their health and healthcare.

A social work plan to promote HIV testing: A social marketing approach.

Many people living with human immunodeficiency virus (HIV) do not know that they are infected. It is important for infected persons to get tested for HIV in order to be diagnosed and medically treated. HIV has no known cure, but it can be controlled and sometimes prevented with proper medical care. The social work profession has ideal positioning to be extraordinarily helpful in work that promotes HIV testing, leading to reducing then eliminating new HIV diagnoses. Social marketing interventions, along with audience segmenting are explained. Specific attention is given to two separate subjects-minority health disparities and impulsive and/or sensation seeking sex practices-to showcase the versatility of social marketing in the promotion of HIV testing. Further ideas about how social workers can participate in these interprofessional social marketing campaigns are provided.

A cluster randomized controlled trial on the effects and costs of advance care planning in elderly care: study protocol.

BACKGROUND: Currently, health care and medical decision-making at the end of life for older people are often insufficiently patient-centred. In this trial we study the effects of Advance Care Planning (ACP), a formalised process of timely communication about care preferences at the end of life, for frail older people. METHODS/DESIGN: We will conduct a cluster randomised controlled trial among older people residing in care homes or receiving home care in the Netherlands. The intervention group will receive the ACP program Respecting Choices® in addition to usual care. The control group will receive usual care only. Participants in both groups will fill out questionnaires at baseline and after 12 months. We hypothesize that ACP will lead to better patient activation in medical decision making and quality of life, while reducing the number of medical interventions and thus health care costs. Multivariate analysis will be used to compare differences between the intervention group and the control group at baseline and to compare differences in changes after 12 months following the inclusion. DISCUSSION: Our study can contribute to more understanding of the effects of ACP on patient activation and quality of life in frail older people. Further, we will gain insight in the costs and cost-effectiveness of ACP. This study will facilitate ACP policy for older people in the Netherlands. TRIAL REGISTRATION: Nederlands Trial Register: NTR4454.

A favorable course of palliative sedation: searching for indicators using caregivers' perspectives.

OBJECTIVE: Comparing characteristics of a favorable sedation course during palliative sedation to a less favorable course based on the reports Dutch physicians and nurses. RESULTS: Cases identified as having a favorable sedation course less often concerned a male patient (P = .019 nurses' cases), reached the intended sedation depth significantly quicker (P < .05 both nurses and physicians' cases), reached a deeper level of sedation (P = .015 physicians' cases), and had a shorter total duration of sedation compared (P < .001 physicians' cases) to patients with a less favorable sedation course. CONCLUSIONS: A favorable course during palliative sedation seems more probable when health care professionals report on a (relatively) shorter time to reach the required depth of sedation and when a deeper level of sedation can be obtained.

Continuous palliative sedation: not only a response to physical suffering.

BACKGROUND: Palliative sedation is a medical intervention aimed at relieving symptoms that can no longer be controlled by conventional treatment. Ample knowledge is available regarding the nature of such symptoms, but there is no in-depth information regarding how health care workers decide about palliative sedation. OBJECTIVE: The study objective was to investigate considerations concerning the indications for continuous palliative sedation (CPS) and issues that influence these considerations. DESIGN: The study consisted of qualitative interviews regarding patients who had recently received CPS. SETTING/SUBJECTS: The study involved physicians and nurses working in general practice, nursing homes, and hospitals. MEASUREMENT: Analyses by a multidisciplinary research team used the constant comparative method. RESULTS: Together with physical symptoms, psychological and existential suffering may combine to produce a refractory state for which other treatment options than CPS were not available or considered inappropriate. A limited life expectancy was by many considered crucial (e.g., to avoid hastening death) and by some less important (e.g., because the patient's suffering was considered to be key). Issues influencing the decision to use CPS related to patient preferences (e.g., dignity, not wanting to experience further suffering) or family issues (impact of suffering on family, family requesting CPS). CONCLUSIONS: The indication for CPS typically originates from physical symptoms and nonphysical problems producing a refractory state in which a patient suffers unbearably. In such states, preferences of patients and families and the life expectancy criterion are weighed against the severity of refractory symptoms. Therefore the use of CPS is not only a response to the physical suffering of patients in the dying phase.

Estimating the potential life-shortening effect of continuous sedation until death: a comparison between two approaches.

CONTEXT: In some cases, physicians estimate that continuous sedation until death may have a life shortening effect. The accuracy of these estimations can be questioned. AIM: The aim of this study is to compare two approaches to estimate the potential life-shortening effect of continuous sedation until death. METHODS: In 2008, 370 Dutch physicians filled out a questionnaire and reported on their last patient who received continuous sedation until death. The potential life-shortening effect of continuous sedation was estimated through a direct approach (question: Did continuous sedation, according to your estimation,hasten the patient's death? If yes: by how much time?)and an indirect approach (estimated life expectancy minus duration of sedation). The intrarater agreement between both approaches was determined with a weighted κ. RESULTS: According to the direct approach, sedation might have had a life-shortening effect in 51% of the cases and according to the indirect approach in 84%.The intrarater agreement between both approaches was fair (weighted κ=0.38). In 10% of all cases, the direct approach yielded higher estimates of the extent to which life had been shortened; in 58% of the cases, the indirect approach yielded higher estimates. CONCLUSIONS: The results show a discrepancy between different approaches to estimate the potential life shortening effect of continuous sedation until death.

Day-to-day care in palliative sedation: survey of nurses' experiences with decision-making and performance.

CONTEXT: Continuous palliative sedation has been the focus of extensive international debates in the field of end-of-life decision making. Although nurses may be important participants in the performance of continuous palliative sedation, research has focused primarily on the role and experience of physicians. Nurses' experiences differ from that of physicians; they more often describe that continuous palliative sedation is used with the intention of hastening death and to have experienced serious emotional burden. Therefore, it is important to understand the experience of nurses in continuous palliative sedation. OBJECTIVE: To describe nurses' experiences with the decision-making and performance of continuous palliative sedation in terminally ill patients. METHODS: Cross-sectional study. In 2008, a structured questionnaire was sent to 576 nurses in six professional home care organizations, ten units for palliative care in nursing homes and in-patient hospices and seven hospitals in the western region of the Netherlands. Respondents provided information about the last patient receiving continuous palliative sedation whom they had cared for. RESULTS: Two-hundred seventy-seven questionnaires were returned and 199 (71.84%) reported a case of continuous palliative sedation. Nurses felt involved in the decision to use sedation in 84% of cases, albeit to a lesser extent in home care (68.75%, p=0.002). They agreed with the performance of continuous palliative sedation in 95.97% of cases and they proposed the use of continuous palliative sedation in 16.16%. Nurses were present at the start of sedation in 81.40% of cases and reported physicians to be present in 45.22%. In 72.77%, arrangements had been made among caregivers about the coordination of health care regarding the sedation. CONCLUSION: Nurses seem to play an important role in the use of continuous sedation. This role is mainly supportive toward physicians and patients during the decision-making process, but shifts to an active performance of sedation, particularly in settings where they explicitly participate as members of a team. Nurses could develop the practice of palliative sedation by anticipating procedural obstacles in the performance of continuous palliative sedation. We recommend them to become more active participants in the decision-making to improve the care of patients receiving continuous palliative sedation.

Pressure during decision making of continuous sedation in end-of-life situations in Dutch general practice.

BACKGROUND: Little is known about pressure from patients or relatives on physician's decision making of continuous palliative sedation. We aim to describe experienced pressure by general practitioners (GPs) in cases of continuous sedation after the introduction of the Dutch practice guideline, using a questionnaire survey. METHODS: A sample of 918 Dutch GPs were invited to fill out a questionnaire about their last patient under continuous sedation. Cases in which GPs experienced pressure from the patient, relatives or other persons were compared to those without pressure. RESULTS: 399 of 918 invite GPs (43%) returned the questionnaire and 250 provided detailed information about their most recent case of continuous sedation. Forty-one GPs (16%) indicated to have experienced pressure from the patient, relatives or colleagues. In GPs younger than 50, guideline knowledge was not related to experienced pressure, whereas in older GPs, 15% with and 36% without guideline knowledge reported pressure. GPs experienced pressure more often when patients had psychological symptoms (compared to physical symptoms only) and when patients had a longer estimated life expectancy. A euthanasia request of the patient coincided with a higher prevalence of pressure for GPs without, but not for GPs with previous experience with euthanasia. GPs who experienced pressure had consulted a palliative consultation team more often than GPs who did not experience pressure. CONCLUSION: One in six GPs felt pressure from patients or relatives to start sedation. This pressure was related to guideline knowledge, especially in older GPs, longer life expectancy and the presence of a euthanasia request, especially for GPs without previous experience of euthanasia.

Considerations of physicians about the depth of palliative sedation at the end of life.

BACKGROUND: Although guidelines advise titration of palliative sedation at the end of life, in practice the depth of sedation can range from mild to deep. We investigated physicians' considerations about the depth of continuous sedation. METHODS: We performed a qualitative study in which 54 physicians underwent semistructured interviewing about the last patient for whom they had been responsible for providing continuous palliative sedation. We also asked about their practices and general attitudes toward sedation. RESULTS: We found two approaches toward the depth of continuous sedation: starting with mild sedation and only increasing the depth if necessary, and deep sedation right from the start. Physicians described similar determinants for both approaches, including titration of sedatives to the relief of refractory symptoms, patient preferences, wishes of relatives, expert advice and esthetic consequences of the sedation. However, physicians who preferred starting with mild sedation emphasized being guided by the patient's condition and response, and physicians who preferred starting with deep sedation emphasized ensuring that relief of suffering would be maintained. Physicians who preferred each approach also expressed different perspectives about whether patient communication was important and whether waking up after sedation is started was problematic. INTERPRETATION: Physicians who choose either mild or deep sedation appear to be guided by the same objective of delivering sedation in proportion to the relief of refractory symptoms, as well as other needs of patients and their families. This suggests that proportionality should be seen as a multidimensional notion that can result in different approaches toward the depth of sedation.

Continuous palliative sedation until death: practice after introduction of the Dutch national guideline.

BACKGROUND: In 2005, a national palliative guideline was launched in The Netherlands. The authors describe the practice of continuous palliative sedation until death (CPS) after the introduction of this guideline. METHODS: In 2008, a random sample of physicians (n=1580) were asked to fill out a questionnaire regarding the last patient in whom they had provided CPS until death. RESULTS: The response was 38%. In all, 82% of the respondents were aware of the existence of the national guideline. Dyspnoea, pain and physical exhaustion were most often mentioned as decisive indications for continuous sedation. The decision to use sedation was discussed with all competent patients, but in 18% this merely involved informing the patient. Life expectancy at the start of continuous sedation was estimated to be less than 2 weeks in 97% of the cases. In 14%, the physicians had felt pressure to start the sedation, predominantly from patients and relatives. Physicians were present at the start of the sedation in 81% of the cases. Midazolam was used to induce the sedation in 92%. Overall, 41% of the physicians estimated that continuous sedation had hastened death to some extent. Most physicians thought that patients' complaints were adequately relieved by continuous sedation, that relatives were satisfied and that a good quality of dying was achieved. INTERPRETATION: Continuous palliative sedation practice in The Netherlands largely reflects the recommendations from the national guideline. Issues needing further attention are the pressure felt by physicians to start continuous sedation and the potential life-shortening effect as mentioned by the physicians.

Continuous palliative sedation for cancer and noncancer patients.

CONTEXT: Palliative care is often focused on cancer patients. Palliative sedation at the end of life is an intervention to address severe suffering in the last stage of life. OBJECTIVES: To study the practice of continuous palliative sedation for both cancer and noncancer patients. METHODS: In 2008, a structured questionnaire was sent to 1580 physicians regarding their last patient receiving continuous sedation until death. RESULTS: A total of 606 physicians (38%) filled out the questionnaire, of whom 370 (61%) reported on their last case of continuous sedation (cancer patients: n=282 [76%] and noncancer patients: n=88 [24%]). More often, noncancer patients were older, female, and not fully competent. Dyspnea (odds ratio [OR]=2.13; 95% confidence interval [CI]: 1.22, 3.72) and psychological exhaustion (OR=2.64; 95% CI: 1.26, 5.55) were more often a decisive indication for continuous sedation for these patients. A palliative care team was consulted less often for noncancer patients (OR=0.45; 95% CI: 0.21, 0.96). Also, preceding sedation, euthanasia was discussed less often with noncancer patients (OR=0.42; 95% CI: 0.24, 0.73), whereas their relatives more often initiated discussion about euthanasia than relatives of cancer patients (OR=3.75; 95% CI: 1.26, 11.20). CONCLUSION: The practice of continuous palliative sedation in patients dying of cancer differs from patients dying of other diseases. These differences seem to be related to the less predictable course of noncancer diseases, which may reduce physicians' awareness of the imminence of death. Increased attention to noncancer diseases in palliative care practice and research is, therefore, crucial as is more attention to the potential benefits of palliative care consultation.

[Palliative sedation largely in accordance with Dutch national guideline]. / Palliatieve sedatie na introductie KNMG-richtlijn.

OBJECTIVE: To evaluate the practice of continuous palliative sedation after the introduction of a national guideline. DESIGN: Investigation by questionnaire. METHOD: In 2008, 1580 physicians were asked to fill out a questionnaire regarding the last patient for whom they had prescribed continuous sedation until death. RESULTS: The response was 38% (n = 606). Eighty-two percent of the respondents were aware of the national guideline. Dyspnoea, pain and physical exhaustion were most often mentioned as the decisive indications for continuous sedation. The decision to use sedation was discussed with all mentally competent patients; in 18% of these cases, the patients had only been informed of the decision. Life expectancy at the start of continuous sedation was estimated to be less than 2 weeks in 97% of the cases. In 14% of the cases, the physicians felt pressured to start the sedation, predominantly by patients and relatives. Physicians were present at the start of sedation in 81% of the cases. Midazolam was used to induce sedation in 92%, and 41% of the physicians estimated that continuous sedation had hastened death to some extent. Most physicians believed that their patients' symptoms had been adequately relieved by continuous sedation, that the relatives were satisfied and that the quality of dying had been good. CONCLUSION: Continuous sedation practice in the Netherlands largely reflects the recommendations of the national guideline. Issues needing further attention are the pressure felt by physicians to start continuous sedation, as well as the possible life-shortening effect of continuous sedation as perceived by some of the physicians.

Does recognition of the dying phase have an effect on the use of medical interventions?

During the dying phase, patients often receive interventions that are not aimed at promoting their comfort. We investigated how recognition of the dying phase affects the use of interventions by comparing patients for whom the dying phase had been recognized with patients for whom it had not been recognized. We included 489 of 613 patients (80%) who died either in a hospital, nursing home, or primary care setting between November 2003 and February 2006. After the death of patients, nurses filled in questionnaires, and patient records were searched for information about therapeutic and diagnostic interventions applied during the dying phase. Caregivers had recognized the dying phase of 380 patients (78%). The number of patients who had received diagnostic interventions during the last three days of life was significantly lower when the dying phase had been recognized (39% vs. 57%) (p = 0.00). Therapeutic interventions were used in similar frequencies in both groups. We conclude that recognition of the dying phase reduces the number of undesirable diagnostic interventions.

Using the LCP: bereaved relatives' assessments of communication and bereavement.

The Liverpool Care Pathway (LCP) is aimed at improving care and communication in the dying phase. The authors studied whether use of the LCP affects relatives' retrospective evaluation of communication and their level of bereavement. An intervention study was conducted. During the baseline period, usual care was provided to dying patients. During the intervention period, the LCP was used for 79% of the patients. In total, bereaved relatives filled in a questionnaire for 57% of the patients, on average 4 months after death. In the intervention period, relatives had lower bereavement levels when compared with relatives in the baseline period (P = .01). Communication was evaluated similarly for both periods. We conclude that LCP use during the dying phase seems to moderately contribute to lower levels of bereavement in relatives.

The effect of the Liverpool Care Pathway for the dying: a multi-centre study.

We studied the effect of the Liverpool Care Pathway (LCP) on the documentation of care, symptom burden and communication in three health care settings. Between November 2003 and February 2005 (baseline period), the care was provided as usual. Between February 2005 and February 2006 (intervention period), the LCP was used for all patients for whom the dying phase had started. After death of the patient, a nurse and a relative filled in a questionnaire. In the baseline period, 219 nurses and 130 relatives filled in a questionnaire for 220 deceased patients. In the intervention period, 253 nurses and 139 relatives filled in a questionnaire for 255 deceased patients. The LCP was used for 197 of them. In the intervention period, the documentation of care was significantly more comprehensive compared with the baseline period, whereas the average total symptom burden was significantly lower in the intervention period. LCP use contributes to the quality of documentation and symptom control.