Caractéristiques de départ et issues chez des patients atteints de COVID-19 hospitalisés dans des unités de soins intensifs à Vancouver (Canada) : série de cas.

CONTEXTE: La pandémie de maladie à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est associée à une mortalité élevée dans les unités de soins intensifs (USI). Nous avons voulu décrire les caractéristiques cliniques et les issues des patients gravement atteints de la maladie à coronavirus 2019 (COVID-19) en contexte canadien. MÉTHODES: Nous avons procédé à l'étude rétrospective d'une série de cas graves d'infection au SRAS-CoV-2 confirmée en laboratoire hospitalisés dans l'une des 6 USI du Vancouver métropolitain, en Colombie-Britannique (Canada), entre le 21 février et le 14 avril 2020. Les données démographiques, les renseignements sur la prise en charge et les résultats ont été recueillis à partir des dossiers médicaux, électroniques ou non, des patients. RÉSULTATS: Entre le 21 février et le 14 avril 2020, 117 patients ont été admis dans une USI avec un diagnostic confirmé de COVID-19. L'âge médian était de 69 ans (écart interquartile [EI] 60­75 ans); et 38 (32,5 %) étaient des femmes. Au moins une comorbidité était présente chez 86 patients (73,5 %). La ventilation mécanique a été nécessaire chez 74 patients (63,2 %). La durée de la ventilation mécanique a été de 13,5 jours (EI 8­22 jours) dans l'ensemble et de 11 jours (II 6­16) chez les patients qui ont reçu leur congé de l'USI. Du tocilizumab a été administré à 4 patients et de l'hydroxychloroquine à 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) étaient décédés, 12 (10,3 %) étaient toujours à l'USI, 16 (13,7 %) avaient obtenu leur congé de l'USI, mais restaient hospitalisés, et 71 (60,7 %) avaient pu retourner à la maison. INTERPRÉTATION: Dans cette étude, la mortalité chez les patients gravement malades de la COVID-19 hospitalisés dans une USI a été moins élevée que chez les patients d'études précédentes. Ces résultats donnent à penser que le pronostic des cas graves de COVID-19 pourrait ne pas être aussi sombre que ce qui avait d'abord été rapporté.

Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series.

BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.

Patterns of social determinants of health associated with drug use among women living with HIV in Canada: a latent class analysis.

BACKGROUND AND AIMS: Identifying typologies of social determinants of health (SDoH) vulnerability influencing drug use practices among women living with HIV (WLWH) can help to address associated harms. This research aimed to explore the association of SDoH clusters with drug use among WLWH. DESIGN: Latent class analysis (LCA) was used to identify the distinct clusters of SDoH. Inverse probability weighting (IPW) was employed to account for confounding and potential selection bias. Associations were analyzed using generalized linear model with log link and Poisson distribution, and then weighted risk ratio (RR) and 95% confidence intervals (CI) were reported. SETTING AND PARTICIPANTS: Data from 1422 WLWH recruited at time-point 1 of the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS, 2013-15), with 1252 participants at 18 months follow-up (time-point 2). MEASUREMENTS: Drug use was defined as use of illicit/non-prescribed opioids/stimulants in the past 6 months. SDoH indicators included: race discrimination, gender discrimination, HIV stigma, social support, access to care, food security, income level, employment status, education, housing status and histories of recent sex work and incarceration. FINDINGS: LCA identified four SDoH classes: no/least SDoH adversities (6.6%), discrimination/stigma (17.7%), economic hardship (30.8%) and most SDoH adversities (45.0%). Drug use was reported by 17.5% and 17.2% at time-points 1 and 2, respectively. WLWH with no/least SDoH adversities were less likely to report drug use than those in economic hardship class (weighted RR = 0.13; 95% CIs = 0.03, 0.63), discrimination/stigma class (weighted RR = 0.15; 95% CIs = 0.03, 0.78), and most SDoH adversities class (weighted RR = 0.13; 95% CIs = 0.03, 0.58). CONCLUSIONS: Social determinants of health vulnerabilities are associated with greater likelihood of drug use, underscoring the significance of addressing interlinked social determinants and drug use through the course of HIV care and treatment.

Clinical heterogeneity of patients with stool samples testing PCR+/Tox- from a two-step Clostridium difficile diagnostic algorithm.

The clinical significance of indeterminate (PCR+/Tox-) results for patients tested with a two-step algorithm for Clostridium difficile infection (CDI) is uncertain. We aimed to evaluate the clinical presentation and 8-week outcomes of patients with indeterminate test results. Patients with stool samples testing positive by PCR and negative by toxin A/B immunoassay between February 1, 2017, and April 30, 2018, were assessed by antimicrobial stewardship program (ASP) clinicians and classified as colonized or infected. Retrospective chart review was performed to obtain outcomes occurring within 8 weeks of testing, including recurrent C. difficile diarrhea, subsequent treatment for CDI, follow-up C. difficile testing, all-cause mortality, and CDI-related complications. In total, 110 PCR+/Tox- patients were evaluated. ASP classified 54% of patients as infected and 46% as colonized. Patients assessed and classified as colonized did not have increased adverse outcomes by 8 weeks compared to those assessed as infected, despite not receiving treatment for CDI. We conclude that PCR+/Tox- patients are heterogeneous with respect to clinical presentation. Negative toxin A/B immunoassay in a two-step algorithm should not be interpreted in isolation to distinguish colonization from infection as many PCR+/Tox- results may be clinically significant for CDI.

Pathways From HIV-Related Stigma to Antiretroviral Therapy Measures in the HIV Care Cascade for Women Living With HIV in Canada.

BACKGROUND: Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada. METHODS: We used baseline survey data from a national cohort of women living with HIV in Canada (n = 1425). Structural equation modeling using weighted least squares estimation methods was conducted to test the direct effects of HIV-related stigma dimensions (personalized, negative self-image, and public attitudes) on ART initiation, current ART use, and 90% ART adherence, and indirect effects through depression and HIV disclosure concerns, adjusting for sociodemographic factors. RESULTS: In the final model, the direct paths from personalized stigma to ART initiation (ß = -0.104, P < 0.05) and current ART use (ß = -0.142, P < 0.01), and negative self-image to ART initiation (ß = -0.113, P < 0.01) were significant, accounting for the mediation effects of depression and HIV disclosure concerns. Depression mediated the pathways from personalized stigma to ART adherence, and negative self-image to current ART use and ART adherence. Final model fit indices suggest that the model fit the data well [χ(25) = 90.251, P < 0.001; comparative fit index = 0.945; root-mean-square error of approximation = 0.044]. CONCLUSIONS: HIV-related stigma is associated with reduced likelihood of ART initiation and current ART use, and suboptimal ART adherence. To optimize the benefit of ART among women living with HIV, interventions should reduce HIV-related stigma and address depression.

Reduction in hospital-associated methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus with daily chlorhexidine gluconate bathing for medical inpatients.

BACKGROUND: Daily bathing with chlorhexidine gluconate (CHG) is increasingly used in intensive care units to prevent hospital-associated infections, but limited evidence exists for noncritical care settings. METHODS: A prospective crossover study was conducted on 4 medical inpatient units in an urban, academic Canadian hospital from May 1, 2014-August 10, 2015. Intervention units used CHG over a 7-month period, including a 1-month wash-in phase, while control units used nonmedicated soap and water bathing. Rates of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization or infection were the primary end point. Hospital-associated S. aureus were investigated for CHG resistance with a qacA/B and smr polymerase chain reaction (PCR) and agar dilution. RESULTS: Compliance with daily CHG bathing was 58%. Hospital-associated MRSA and VRE was decreased by 55% (5.1 vs 11.4 cases per 10,000 inpatient days, P = .04) and 36% (23.2 vs 36.0 cases per 10,000 inpatient days, P = .03), respectively, compared with control cohorts. There was no significant difference in rates of hospital-associated Clostridium difficile. Chlorhexidine resistance testing identified 1 isolate with an elevated minimum inhibitory concentration (8 µg/mL), but it was PCR negative. CONCLUSIONS: This prospective pragmatic study to assess daily bathing for CHG on inpatient medical units was effective in reducing hospital-associated MRSA and VRE. A critical component of CHG bathing on medical units is sustained and appropriate application, which can be a challenge to accurately assess and needs to be considered before systematic implementation.

Incidence and Costs of Clostridium difficile Infections in Canada.

Background. Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods. We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results. There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions. The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs.

Qualitative evaluation and economic estimates of an infection control champions program.

BACKGROUND: In many North American hospitals, conventional infection control operational models often struggle to provide sufficient support to frontline health care workers. The objective of this study was to describe a sustainable infection control champion (ICC) program based on findings from focus groups. METHODS: A distributed model of infection control was established by placing infection prevention and control-trained ICCs in 3 Canadian hospitals for a period of 12 months. Subsequently, semistructured focus groups were conducted to describe overall feasibility and impeding and critical factors affecting sustainability. An economic estimate of the ICC program compared with the cost of hiring a new infection control practitioner was also calculated. RESULTS: Focus group participants considered the program feasible. Barriers included lack of time and staff turnover. Themes critical for the successful implementation of an ICC program included defined ICC roles and goals, adequate support and resources for the ICC, engagement with all levels of staff, flexible structure, and program evaluation. The cost per bed of the ICC program was less than the cost per bed of hiring a new infection control practitioner. CONCLUSION: A distributed model of providing infection prevention and control services may have benefit when hospital infection control teams are underresourced, as is often the case. Several key factors are needed for the successful implementation of an ICC program.

DETERMINANTS OF CUTANEOUS INJECTION-RELATED INFECTIONS AMONG INJECTION DRUG USERS AT AN EMERGENCY DEPARTMENT.

INTRODUCTION: Cutaneous injection-related infections (CIRI) are a primary reason injection drug users (IDU) access the emergency department (ED). METHODOLOGY: Using Cox proportional hazard regression, we examined predictors of ED use for CIRI, stratified by sex, among 1083 supervised injection facility (SIF) users. RESULTS: Over a four-year period, 289 (27%) visited the ED for CIRI, yielding an incidence density for females of 23.8 (95% confidence interval (CI): 19.3 - 29.0) and males of 19.2 per 100 person-years (95% CI: 16.7 - 22.1). Factors associated with ED use for CIRI among females included residing in the Downtown Eastside (DTES) (adjusted hazard ratio [AHR] = 2.06 [1.13 - 3.78]) and being referred to hospital by SIF nurses (AHR = 4.48 [2.76 - 7.30]). Among males, requiring assistance with injection (AHR = 1.38 [1.01 - 1.90]), being HIV-positive (AHR = 1.85 [1.34 - 2.55]), and being referred to hospital by SIF nurses (AHR = 2.97 [1.93 - 4.57]) were associated with an increased likelihood of an ED visit for CIRI. CONCLUSION: These results suggest SIF nurses have facilitated referral of hospital treatment for CIRI, highlighting the need for continued development of efficient and collaborative efforts to reduce the burden of CIRI.

Determinants of hospitalization for a cutaneous injection-related infection among injection drug users: a cohort study.

BACKGROUND: Cutaneous injection-related infections (CIRI) are a primary reason individuals who inject drugs (IDU) are hospitalized. The objective of this study was to investigate determinants of hospitalization for a CIRI or related infectious complication among a cohort of supervised injection facility (SIF) users. METHODS: From 1 January 1 2004 until 31 January 2008, using Cox proportional hazard regression, we examined determinants of hospitalization for a CIRI or related infectious complication (based on ICD 10 codes) among 1083 IDU recruited from within the SIF. Length of stay in hospital and cost estimates, based on a fully-allocated costing model, was also evaluated. RESULTS: Among hospital admissions, 49% were due to a CIRI or related infectious complication. The incidence density for hospitalization for a CIRI or related infectious complication was 6.07 per 100 person-years (95% confidence intervals [CI]: 4.96 - 7.36). In the adjusted Cox proportional hazard model, being HIV positive (adjusted hazard ratio [AHR] = 1.79 [95% CI: 1.17 - 2.76]) and being referred to the hospital by a nurse at the SIF (AHR = 5.49 [95% CI: 3.48 - 8.67]) were associated with increased hospitalization. Length of stay in hospital was significantly shorter among participants referred to the hospital by a nurse at the SIF when compared to those who were not referred (4 days [interquartile range {IQR}: 2-7] versus 12 days [IQR: 5-33]) even after adjustment for confounders (p = 0.001). CONCLUSIONS: A strong predictor of hospitalization for a CIRI or related infectious complication was being referred to the hospital by a nurse from the SIF. This finding indicates that nurses not only facilitate hospital utilization but may provide early intervention that prevents lengthy and expensive hospital visits for a CIRI or related infectious complication.

Harmful microinjecting practices among a cohort of injection drug users in vancouver Canada.

OBJECTIVES: We sought to identify factors associated with harmful microinjecting practices in a longitudinal cohort of IDU. METHODS: Using data from the Vancouver Injection Drug Users Study (VIDUS) between January 2004 and December 2005, generalized estimating equations (GEE) logistic regression was performed to examine sociodemographic and behavioral factors associated with four harmful microinjecting practices (frequent rushed injecting, frequent syringe borrowing, frequently injecting with a used water capsule, frequently injecting alone). RESULTS: In total, 620 participants were included in the present analysis. Our study included 251 (40.5%) women and 203 (32.7%) self-identified Aboriginal participants. The median age was 31.9 (interquartile range: 23.4-39.3). GEE analyses found that each harmful microinjecting practice was associated with a unique profile of sociodemographic and behavioral factors. DISCUSSION: We observed high rates of harmful microinjecting practices among IDU. The present study describes the epidemiology of harmful microinjecting practices and points to the need for strategies that target higher risk individuals including the use of peer-driven programs and drug-specific approaches in an effort to promote safer injecting practices.

Recent incarceration linked to cutaneous injection-related infections among active injection drug users in a Canadian setting.

Cutaneous injection-related infections (CIRI), such as abscesses and cellulitis, are the cause of a substantial burden of morbidity and mortality among injection drug users (IDU). The possible contribution of exposure to correctional environments to CIRI risk has not been fully investigated. Thus, we sought to test the possible relationship between incarceration and CIRI using data from a community-based sample of IDU. Data for these analyses was from the Scientific Evaluation of Supervised Injecting (SEOSI) cohort, linked with administrative records of a local ED in Vancouver, Canada. Using longitudinal analysis we assessed the relationship between the number of ED visits for CIRI care and recent incarceration in a multivariate model including information on possible confounders. Between June 2004 and December 2006, 901 individuals were eligible for our analysis. Of these, 214 (9.6%) visited the ED for CIRI care at least once during the study period. The incidence of ED care for CIRI was 72.9 per 100 person years. In a multivariate model, recent incarceration was associated with a greater number of ED visits for CIRI care (adjusted relative rate = 1.56, 95% confidence interval: 1.31-1.85, P < 0.001). The need for ED treatment for CIRI was common among a sample of local IDU. Exposure to correctional environments was an independent risk factor for visiting the ED for CIRI care, suggesting improvements in infection control in local prisons is urgently needed.

Assisted injection in outdoor venues: an observational study of risks and implications for service delivery and harm reduction programming.

BACKGROUND: Assisted injection and public injection have both been associated with a variety of individual harms including an increased risk of HIV infection. As a means of informing local IDU-driven interventions that target or seek to address assisted injection, we examined the correlates of receiving assistance with injecting in outdoor settings among a cohort of persons who inject drugs (IDU). METHODS: Using data from the Vancouver Injection Drug Users Study (VIDUS), an observational cohort study of IDU, generalized estimating equations (GEE) were performed to examine socio-demographic and behavioural factors associated with reports of receiving assistance with injecting in outdoor settings. RESULTS: From January 2004 to December 2005, a total of 620 participants were eligible for the present analysis. Our study included 251 (40.5%) women and 203 (32.7%) self-identified Aboriginal participants. The proportion of participants who reported assisted injection outdoors ranged over time between 8% and 15%. Assisted injection outdoors was independently and positively associated with being female (Adjusted Odds Ratio (AOR) = 1.74, 95% Confidence Intervals (CI): 1.21-2.50), daily cocaine injection (AOR = 1.70, 95% CI: 1.29-2.24), and sex trade involvement (AOR = 1.44, 95% CI: 1.00-2.06) and was negatively associated with Aboriginal ethnicity (AOR = 0.58, 95% CI: 0.41-0.82). CONCLUSIONS: Our findings indicate that a substantial proportion of local IDU engage in assisted injecting in outdoor settings and that the practice is associated with other markers of drug-related harm, including being female, daily cocaine injecting and sex trade involvement. These findings suggest that novel interventions are needed to address the needs of this subpopulation of IDU.

Determinants of cutaneous injection-related infection care at a supervised injecting facility.

PURPOSE: To evaluate the factors associated with receiving cutaneous injection-related infection (CIRI) care among a representative cohort of supervised injecting facility (SIF) users. METHODS: Data were collected biannually as part of a prospective cohort, the Scientific Evaluation of Supervised Injection study. Kaplan-Meier methods and Cox proportional hazards regression with recurrent events were used to examine incidence and factors associated with CIRI care, respectively. RESULTS: One thousand eighty individuals were recruited between December 1, 2003 and January 31, 2008. The incidence density of participants receiving CIRI care was 22.0 per 100 person-years (95% confidence interval [CI]: 19.6-24.6). In the adjusted Cox proportional hazard model, female sex (adjusted hazard ratio [AHR]=1.87 [95% CI: 1.32-2.64]), unstable housing (AHR=1.39 [95% CI: 1.02-1.88]), and daily heroin injection (AHR=1.52 [95% CI: 1.13-2.04]) were independently associated with receiving CIRI care at the SIF. CONCLUSIONS: These results describe who is more likely to receive CIRI care, which is of use to those engaged with policy and practice of treatment regimens involving this population.

Incidence and determinants of initiation into cocaine injection and correlates of frequent cocaine injectors.

PURPOSE: To investigate the incidence and correlates of cocaine injection initiation and the impacts of daily cocaine injection among a cohort of injection drug users. METHODS: Among 1603 participants, from May 1996 to December 2005, risk factors for initiation of cocaine injection among baseline heroin users were determined by Cox proportional hazards regression and correlates of daily cocaine injection by generalized estimating equations. FINDINGS: Of the 238 individuals who had never injected cocaine, 200 (84%) had at least one follow-up visit and 121 (61%) consequently initiated into cocaine injection, yielding an incidence density of initiation into cocaine injection of 21.9% (95% confidence interval (CI): 17.9-25.8) per 100 person-years. In a multivariate model, Downtown Eastside (DTES) residence (adjusted hazard ratio (AHR)=2.46, 95% CI: 1.68-3.60), incarceration (AHR=1.50, 95% CI: 1.01-2.24), requiring help injecting (AHR=1.57, 95% CI: 0.99-2.49), and binge drug use (AHR=1.82, 95% CI: 1.22-2.73) remained associated with initiation into cocaine injection. DTES residence (adjusted odds ratio (AOR)=1.99, 95% CI: 1.62-2.46), unstable housing (AOR=1.28, 95% CI: 1.04-1.53), incarceration (AOR=1.29, 95% CI: 1.04-1.60), sex trade involvement (AOR=1.46, 95% CI: 1.15-1.85), requiring help injecting (AOR=2.11, 95% CI: 1.73-2.58)), borrowing syringes (AOR=1.81, 95% CI: 1.35-2.43) and binge drug use (AOR=2.16, 95% CI: 1.81-2.58) were independently associated with daily cocaine injection. CONCLUSIONS: The baseline prevalence and subsequent incidence of initiation into cocaine injection was high. Daily cocaine injection was independently associated with a number of health and social harms, including elevated HIV risk behavior.

Risk factors for developing a cutaneous injection-related infection among injection drug users: a cohort study.

BACKGROUND: Cutaneous injection-related infections (CIRI), such as abscesses and cellulitis, are common and preventable among injection drug users (IDU). However, risk factors for CIRI have not been well described in the literature. We sought to characterize the risk factors for current CIRI among individuals who use North America's first supervised injection facility (SIF). METHODS: A longitudinal analysis of factors associated with developing a CIRI among participants enrolled in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort between January 1, 2004 and December 31, 2005 was conducted using generalized linear mixed-effects modelling. RESULTS: In total, 1065 participants were eligible for this study. The proportion of participants with a CIRI remained under 10% during the study period. In a multivariate generalized linear mixed-effects model, female sex (Adjusted Odds Ratio (AOR) = 1.68 [95% Confidence Interval (CI): 1.16-2.43]), unstable housing (AOR = 1.49 [95% CI: 1.10-2.03]), borrowing a used syringe (AOR = 1.60 [95% CI: 1.03-2.48]), requiring help injecting (AOR = 1.42 [95% CI: 1.03-1.94]), and injecting cocaine daily (AOR = 1.41 [95% CI: 1.02-1.95]) were associated with an increased risk of having a CIRI. CONCLUSION: CIRI were common among a subset of IDU in this study, including females, those injecting cocaine daily, living in unstable housing, requiring help injecting or borrowing syringes. In order to reduce the burden of morbidity associated with CIRI, targeted interventions that address a range of factors, including social and environmental conditions, are needed.