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1421.
  • Welin, Amanda, 1983- (författare)
  • Survival strategies of Mycobacterium tuberculosis inside the human macrophage
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Mycobacterium tuberculosis (Mtb) is the bacterium responsible for tuberculosis (TB). For decades, it was believed that TB was a disease of the past, but the onset of the HIV epidemic resulting in a greatly increased number of TB cases, the emergence of antibiotic resistant Mtb strains, and the relative ineffectiveness of the BCG vaccine have put TB back on the agenda. With almost two million people being killed by TB each year, the World Health Organization has declared it a global emergency. TB is an especially big issue in low-income countries, where crowded living conditions accelerates spread of the disease, and where access to health care and medication is problematic. Mtb spreads by aerosol and infects its host through the airways. The bacterium is phagocytosed by resident macrophages in the lung, and when successful is able to replicate inside these cells, which are actually designed to kill invading microbes. Mtb is able to evade macrophage responses in part by inhibiting the fusion between the phagosome in which it resides and bactericidal lysosomes, as well as by dampening the acidification of the vacuole. The initial macrophage infection results in a pro-inflammatory response and the recruitment of other cells of the innate and adaptive immune systems, giving rise to the hallmark of Mtb infection – the granuloma. It is believed that in up to 50 % of exposed individuals, however, the infection is cleared without the involvement of the adaptive immune system, indicating that the innate immune system may be able to control or clear the infection if activated appropriately. This thesis focuses on the interaction between the host macrophage and Mtb, aiming to understand some of the mechanisms employed by the bacterium to evade macrophage responses to enable replication and spread to new host cells. Furthermore, mechanisms used by the macrophage to keep the infection under control were studied, and a method that could be used to measure the replication of the bacilli inside macrophages in vitro in an efficient way was developed. We found that a mycobacterial glycoprotein, mannose-capped lipoarabinomannan (ManLAM), which is shed from the bacilli during phagocytosis by macrophages, integrates into membrane raft domains of the host cell membrane via its GPI anchor. This integration leads to an inhibition of phagosomal maturation. Subsequently, we developed a luciferase-based method by which intracellular replication of Mtb as well as viability of the host macrophage could be measured in a rapid, inexpensive and quantitative way in a 96-well plate. This method could be used for drug screening as well as for studying the different host and bacterial factors that influence the growth of Mtb inside the host cell. Using this method, we discovered that infection of macrophages with Mtb at a low multiplicity of infection (MOI) led to effective control of bacterial growth by the cell, and that this was dependent on functional lysosomal proteases as well as phagosomal acidification. However, we found no correlation between controlled bacterial growth and the translocation of late endosomal membrane proteins to the phagosome, showing that these markers are poor indicators of phagosomal functionality. Furthermore, we discovered that infection of macrophages with Mtb at a higher MOI led to replication of the bacilli accompanied by host cell death within a few days. We characterized this cell death, and concluded that when replication of Mtb inside macrophages reaches a certain threshold and the bacteria secrete a protein termed ESAT-6, necrotic cell death of the host cell occurs. However, although the bacilli activated inflammasome complexes in the host cell and IL-1β was secreted during infection of macrophages, Mtb infection did not induce either of the recently characterized inflammasome-related cell death types pyroptosis or pyronecrosis. Thus, we have elucidated some of the strategies that Mtb uses to be able to survive and replicate inside the macrophage and spread to new cells, as well as studied the conditions under which the host cell is able to control infection. This knowledge could be used in the future for developing drugs that boost the innate immune system or targets bacterial virulence factors in the macrophage.
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1422.
  • Wenemark, Marika, 1968- (författare)
  • The respondent’s perspective in health-related surveys
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Declining response rates are threatening the usefulness of and confidence in survey data. Survey practitioners have therefore studied why nonrespondents refuse to respond and have tried to counter the declining response rates by intensified follow-up methods. Such efforts sometimes yield negative reactions among respondents. This thesis focuses on the respondent’s perspective in self-administered health-related surveys. The aim was to investigate positive and negative aspects that respondents experience when participating in surveys, to study factors that could increase motivation and to study possibilities to increase response rates in a way that promotes data quality as well as positive experiences among respondents. Self-Determination Theory is a motivation theory that was used as a theoretical framework.Paper I is a study regarding two self-administered health questionnaires among patients in 20 intervention groups in 18 Swedish hospitals. Paper II is a qualitative analysis of data from telephone interviews with respondents to a self-administered health-related survey of the population in the county of Östergötland. Paper III is a randomized experiment in a self-administered survey of a random sample of parents in the municipality of Stockholm. Paper IV is an experimental study concerning a self-administered health questionnaire in a random sample of the general adult population in the county of Östergötland.The results from paper I show that questionnaire length and ease of response were not crucial arguments in choosing between two health questionnaires for use in routine health care. Instead, the most common motives for the choice concerned aspects of the questions’ comprehensiveness and ability to describe the health condition. Respondent satisfaction as described by respondents in paper II includes being able to give correct and truthful information as well as reflection and new insights from the questions. Respondent burden includes experiences of being manipulated or controlled by the researcher as well as worry, anxiety or sadness caused by the questions. Experiences of satisfaction and burden differed depending on the respondents’ primary motive for participating in surveys. The findings of paper III illustrate that the use of lottery tickets as incentives to parents may be less valuable or even harmful as a means of increasing response rates. In paper IV a survey design inspired by Self-Determination Theory yielded higher satisfaction among respondents and improved response rates with similar or better data quality compared with a standard design.Focusing on the respondents’ perspective provided important new knowledge. The results show a broad spectrum of positive as well as negative aspects of survey participation. The results support Self-Determination Theory as a useful theoretical framework for studying motivation in survey research and an interesting additional source to provide ideas on how to design surveys with the potential to motivate respondents. The results suggest that it is possible to improve response rates in a way that promotes data quality as well as positive experiences among the respondents.
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1423.
  • Wennberg, Birgitta, 1956- (författare)
  • Keeping track of time : Daily time management, participation, and time-related interventions for children, adolescents, and young adults with neurodevelopmental disorders
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The overall aim of this thesis was to investigate daily time management (DTM) and time-related interventions aiming to enhance participation in everyday activities among school-age children and young adults with neurodevelopmental disorders.In study I, experiences of participation when using time assistive devices (TADs) in daily activities were investigated from the perspective of young adults (aged 17–37) with intellectual disabilities (ID) (n = 9), using semi structured interviews. In studies II and IV, a new multimodal time-related intervention consisting of psychoeducation, compensation with TADs and time-skills training, was investigated in children aged 9–15 with attention-deficit/hyperactivity disorder (ADHD). Study II was a randomized controlled trial (RCT) with an intervention group (n = 19) and a control group (n = 19). The aim of study III was to describe DTM, time processing ability (TPA) and self-rated autonomy in children aged 9–15 with ADHD (n = 47), compared to children with ID (n = 47) and typically developing (TD) children (n = 47). In study IV, occupational performance and satisfaction were evaluated (n = 27). In studies II, III and IV, a source for data collection included assessment, proxy report and self-reports.Using TADs (study I) increased participation in activities in all areas of daily life: self-care, activities at work or school and leisure time activities. A feeling of having more control led to health benefits. Participants described participation restrictions related to attitudes from their social network towards participation and attitudes towards the use of TADs from the individuals themselves. Study II showed that the children in the intervention group increased their TPA significantly more compared to the control group, mostly in terms of time orientation. The parents in the intervention group rated their children’s DTM as significantly more improved compared to the parents of the children in the control group. However, according to the children themselves, there was no statistically significant improvement in their DTM. The psychoeducation for parents and school staff did not increase children’s TPA and DTM on its own. The majority of parents and children (study IV) rated the children’s occupational performance and satisfaction significantly higher at follow-up than at baseline. In general, children rated their occupational performance and satisfaction higher than their parents did. Most goals decided by the children and their parents involved daily routines and time orientation. Study III showed that children with ADHD and children with ID had significantly lower TPA, DTM and autonomy compared to TD children. Children with ADHD showed higher levels of self-rated autonomy compared to children with ID, but the reverse was found in DTM. However, there was significant diversity among children with ADHD and children with ID, which was not explained by age. Some children had difficulties at every level of TPA, while others were skilled at every level. The level of self-rated autonomy followed the level of TPA.In conclusion, this thesis revealed that children with ADHD and ID have the same overall pattern of TPA but may have a delayed TPA, which affects their DTM and autonomy, and thereby also influences their participation in daily activities. The results show that a multimodal time-related intervention using TADs and time-skills training could increase TPA and DTM in children with ADHD aged 9–15 years with time deficits. Experiences from young adults with ID also show increased participation in daily activities and health benefits using TADs. It is recommended that TPA and DTM should be measured to identify difficulties in TPA and DTM in children with ADHD and to offer tailored time-related interventions in addition to medication.
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1424.
  • Wermelin, Karin, 1977- (författare)
  • Surface bound bisphosphonate for implant fixation in bone
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • During the surgical preparation of bone, prior to insertion of an implant, bone will be traumatized which leads to local resorption. Consequently, early implant fixation might be reduced. Impaired early fixation, as evidenced by radiostereometry, has been associated with increased risk of late loosening. Bisphosphonates are known to inhibit bone resorption by osteoclasts and have shown to increase implant fixation when administered systemically or locally directly at the bone prior to implant insertion.A method to bind bisphosphonates directly to the implant was developed. Stainless steel screws were coated with crosslinked fibrinogen, serving as an anchor for bisphosphonate attachment. The screws were inserted in the tibial metaphysis in rats and implant fixation was analyzed with pullout measurements. Bisphosphonate coated screws turned out to have 28 % higher pullout force at 2 weeks compared to control screws with the fibrinogen coating only. The next experiment was designed to measure at what stage in the healing process the strongest bisphosphonate effect was gained. Bisphosphonate coated screws were expected to reduce the resorption of the traumatized bone. However, no decreased fixation was found in the control group. Instead, the fixation increased with time, and so did the effect of the bisphosphonates. At 8 weeks, the pullout force was twice as high for screws with bisphosphonate compared to control screws. By histology at 8 weeks, a bone envelope was found around bisphosphonate coated screws but absent around control screws. Thus, the anti catabolic action of the bisphosphonate resulted in an increased amount of bone surrounding the bisphosphonate screws.Titanium is generally considered to be better fixated in bone compared to stainless steel. The coating technique was found to be applicable on titanium as well, again with improved fixation.A majority of fractures occur in osteoporotic bone. Despite the relatively low amount of bisphosphonates at the screws, the bisphosphonate coating improved implant fixation at 2 weeks also in rats made osteoporotic by ovariectomy.In conclusion, bisphosphonates bound to titanium or stainless steel screws coated with fibrinogen increased fixation in bone, in rats. These results suggest that the bisphosphonate and fibrinogen coating might improve the fixation of screw shaped implants and possibly also arthroplasties, in humans.
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1425.
  • West, Janne (författare)
  • Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear.In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation.The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions.One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration.This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem.This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.
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1426.
  • Westberg, Håkan (författare)
  • Chemical exposures, biological monitoring and cancer risks in Swedish aluminium foundries and remelting plants
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In aluminium foundries and remelting plants, a wide range of chemical agents are formed and emitted, including some highly toxic organochlorine compounds. This thesis explores emissions and exposures, as well as worker risk of porphyria and cancer.During addition of hexachloroethane (HCE) for degassing of the melt, the major findings of organochlorine compounds were hexachlorobenzene (4,300 μg/g HCE) and octachlorostyrene (780 μg/g HCE).In sand, die- and static-die casting aluminium foundries, the total dust concentrations varied up to 93 mg/m3. The aluminium exposures were generally low (< 0.5 mg/m3). For crystalline quartz, 0.1 mg/m3 was exceeded only occasionally. The levels of minor alloy metals including lead, were low (<0.01 mg/m3). At different core production methods, high levels of dimethylethylarnine, aniline and furfuryl alcohol were observed. In die-casting, 33% of the mineral oil mist levels exceeded 1 mg/m3.For smelters, the use of HCE as degassing agent, caused increased plasma levels of hexachlorobenzene (HCB) and octachlorostyrene (OCS) compared to controls. A difference in porphyrins, mainly attributed to enhanced concentrations of coproporphyrins, especially coproporphyrin III, was also noted.In a cohort study of 6,454 workers from seven aluminium foundries and three remelting plants, no overall increased risk for cancer among male and female workers was found. Elevated risks were however seen for lung cancer, anorectal and sinonasal cancer. For sand casting workers, a statistically significant increase in lung cancer morbidity was seen for the long-term employed workers.Based on a statistical model, cumulative total dust and crystalline quartz mg/m3 * years were assessed for 46 cases and 322 controls in a nested case-control study within the cohort. A non-significant increase in the relative risk was observed with increasing dose. The odds ratio for dust was 2.2 for the high exposure group (>29 mg/m3 * year). A similar trend was seen for crystalline quartz.
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1427.
  • Westerberg, Johanna, 1971- (författare)
  • Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cholesteatomas are bone destructive expansions of keratinizing squamous epithelium in the middle ear and temporal bone. Today, surgery is the only treatment. There are several controversies regarding cholesteatomas, including the definition, the pathogenesis and the surgical method. Intense efforts have been made searching for a comprehension of the cholesteatoma process at a cellular and molecular level. Recurrent infections and inflammation seem to be contributing factors for the cholesteatomas to expand. The innate immunity, essential to keep a healthy middle ear environment and to protect the middle ear from intruding pathogens, is therefore a matter of interest.In this thesis, results are presented from a cohort of cholesteatoma surgeries in Östergötland from a 16-year period. A group of patients also filled in a questionnaire to assess changes in health-related quality of life (HRQoL) after surgery. According to the findings in this thesis, the residual and recurrence frequencies are low, and the hearing and HRQoL are improved in the majority of cases.This thesis also presents an investigation of the innate immunity in ears with acquired cholesteatoma, in comparison with healthy controls. The expression of mRNA of toll-like receptors 2 and 4, participants of the Janus kinase/signal transducer and activator of transcription pathway, and nitric oxide synthases in middle ear mucosa, were investigated with quantitative polymerase chain reaction. An investigation of nitric oxide (NO) in the middle ear, with chemiluminescence measurements, is also presented.A derangement of the innate immune system is seen in ears with cholesteatoma, which supports the idea that the innate immunity participates in the cholesteatoma process, though the underlying mechanisms are still unclear. The suggestion of NO production in the middle ear sheds light on NOs possible participation in the healthy middle ear environment.
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1428.
  • Westerlind, Björn, 1961- (författare)
  • Geriatric Aspects of Frail Nursing Home Residents : A Swedish cohort study
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The number and proportion of older people are increasing in Sweden as well as throughout the western world. Older people with increasing assistance needs that can no longer be met in their own home need institutional long-term care in nursing homes. A successive reduction of nursing home beds in combination with a future demographic development with a rapidly increasing number of older people will lead to higher demands on future medical care in nursing homes. Consequently, increased knowledge about the medical needs of nursing home residents is of great value.Objectives: This thesis explores some important geriatric aspects of frail nursing home residents. The specific aims was to characterise the population of nursing home residents, to explore the prevalence of anaemia, paying particular attention to risk factors and mortality, to investigate associations between falls and use of possible fall risk drug classes and to estimate the prevalence of diagnostic failure of cognitive impairment and to investigate whether diagnostic failure was associated with impaired medical care.Methods: All data originate from SHADES (the Study of Health and Drugs in Elderly nursing home residents in Sweden), a prospective cohort study that included nursing home residents at 12 nursing homes situated in three municipalities in southern Sweden between 2008 and 2011. The subjects were followed every six months with data collection from medical records concerning medications, diagnoses, hospital referrals and mortality, examinations including blood sample analyses, assessments with validated rating scales for cognitive evaluation, depression, risk of pressure ulcers, malnutrition or falls, and the need for care was rated through a questionnaire.Results: SHADES included a total of 428 subjects with a mean age of 85 years, of whom 71% were women. They demonstrated comorbidity with a mean of three registered medical diagnoses, and polypharmacy with a mean of seven regularly used drugs. More than half of the sample (60%) were at risk of malnutrition and one third were at risk of developing pressure ulcers. A set of single items from the performed risk assessments was found to be important in understanding frailty and need for care. One third of the women and half of the men had anaemia. For the men, anaemia was associated with significantly higher mortality. Haemoglobin decline was also associated with higher mortality. Almost everyone (93%) had an increased fall risk and 62% had fallen during the last year. There was an association between falls during the last year and regular use of non-benzodiazepine hypnotics. In the older age group there was also an association between these drugs and serious falls the next 6 months. Dementia was previously diagnosed in 42%. However, among subjects without a dementia diagnosis, 72% were cognitively impaired (Mini Mental State Examination <24). These subjects were significantly older, did not get anti-dementia treatment and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, possibly indicating heart failure. Their risks of malnutrition and pressure ulcers were similar to the dementia group.Conclusions: Nursing home residents are generally frail. Anaemia is associated with higher mortality among men. The fall risk is generally high and use of non-benzodiazepine hypnotics is associated with a higher occurrence of falls. Cognitive impairment is undiagnosed in half of the cases and may indicate underlying heart failure. Consequently, regular medical follow-ups in this population are proposed to include blood count, drug review, and cognitive evaluation. In the case of cognitive impairment, exclusion of underlying disease such as heart failure should be considered.
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1429.
  • Whiss, Per A., 1966- (författare)
  • Platelet adhesion and P-selectin surface expression
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Upon injury in a blood vessel, platelets become activated and adbere to prevent blood loss. Activated platelets express adhesion molecules on their surface that also make leukocytes adhere to the injury. One such molecule, which also is expressed on endothelium, is the glycoprotein P-selectin. The present studies were focused on how soluble factors and surfaces can affect P-selectin surface expression on human platelets.This thesis presents an enzyme-linked immunosorbent assay (ELISA) application to study platelet expression and release of P-selectin. The well-known platelet activators collagen, epinephrine, ADP, ristocetin, PMA, and thrombin induced surface expression of P-selectin with different potency and time-dependency in vitro. One of the most powerful platelet activators, thrombin, rapidly mediated both surface expression and release. The surface expression decreased after a short peak upon maximal thrombin-activation. The protein kinase C activator PMA induced surface expression equivalently to thrombin but the release of Pselectin was less as compared to thrombin. Nitric oxide (NO) donors, which mimic a vessel wall mechanism to inhibit platelet activation, decreased expression and release of P-selectin upon activation. Adenosine, another agent that is produced in vivo, acted in concert with NO and totally inhibited P-selectin expression induced by thrombin. NO and adenosine act by increasing the second messengers cGMP and cAMP, respectively.The effects of an infusion of nicotine on platelet P-selectin expression were studied in nicotine users with normal and impaired renal function. After a peak directly after infusion, the plasma concentration of nicotine declined towards the basal level and the level of NO-products was lower as compared to baseline 2 h after infusion. At the same time, P-selectin expression induced by weak activators, but not by thrombin, increased in both groups. A transient and weak inhibition of collagen-induced platelet aggregation was observed directly after infusion. Studies in vitro showed that nicotine per se inhibits P-selectin expression. Thus, nicotine appears to initially inhibit and then increase platelet activation in vivo.The adhesion of platelets to surfaces that can be exposed upon vessel wall injury and the subsequent expression of P-selectin were found to be dependent on divalent cations. Mg2+ dose-dependently increased platelet adhesion to both collagen and fibrinogen in the physiological range, but supraphysiological concentrations decreased the adhesion to fibrinogen. Ca2+ did only increase platelet adhesion to fibrinogen. Platelet adhesion to collagen caused more expression of P-selectin than adhesion to fibrinogen. Thus, the surface and the access of divalent cations regulate platelet adhesion and P-selectin surface expression.In summary, multiple factors rep1late and affect platelet adhesion and P-selectin surface expression. The methods presented in this thesis are suitable for studies to further understand and make pharmacological modulation possible of these complex mechanisms and consequences.
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1430.
  • Wibault, Johanna, 1978- (författare)
  • Neck disability in patients with cervical radiculopathy and evaluation of structured postoperative physiotherapy
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Non-surgical and surgical approaches to treatment are used in patients with cervical radiculopathy (CR) due to disc disease. Overall, good effects of surgery have been reported on arm pain and neurological symptoms. However, the effects on neck functioning are more uncertain. Studies have shown persistent activity limitations; participation restrictions; and impairments in neck-related body functions after surgery. Structured physiotherapy combining neck-specific exercises with a behavioural approach has been suggested as treatment before as well as after surgery to improve clinical outcomes in patients with CR. Randomized clinical trials of postoperative physiotherapy to inform evidence-based clinical guidelines for the treatment of patients with CR are lacking.The overall aim of the thesis was to investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioural approach compared to standard postoperative approach in patients with CR. A further aim was to evaluate the  contribution of different aspects of neck-related body functions and mental functions on preoperative neck disability in these patients.A total of 202 patients with CR who were scheduled for surgery were recruited, and randomized preoperatively to either structured postoperative physiotherapy, or standard postoperative approach. Standard postoperative approach was in accordance with Swedish postoperative care, and may have included pragmatic physiotherapy after surgery when needed. Patients were evaluated with a set of questionnaires and clinical examinations before surgery and at 3 and 6 months after surgery. Outcomes included patient-reported measures of pain, neck functioning, global outcome, clinical evaluation of neckrelated body functions, self-efficacy and coping strategies, as well as expectation fulfilment and enablement. Differences between treatment groups were investigated in complete case and per-protocol approaches (Paper III & IV). A sub-sample of patients with CR who were scheduled for surgery were also compared with neck-healthy individuals for assessment of head repositioning accuracy with a cervical range of motion device (Paper I). In patients with CR who were scheduled for surgery, associations between preoperative measures of neck-related body functions, mental functions, and other contextual factors with patientreported neck disability were studied (Paper II).With the exception of greater expectation fulfilment in patients who received structured postoperative physiotherapy (p = 0.01), there were no differences between the treatment groups in outcomes at 6 months after surgery. There were no differences reported for changes in  outcomes from before surgery to 6 months after surgery between the groups, but all outcomes significantly improved from baseline in both groups (p<0.001) (Paper III & IV). However, global outcome and frequency of neck pain improved during the postoperative period only in patients who received structured postoperative physiotherapy (p< 0.01) (Paper III). Six months after surgery, patients with at least 50% attendance to treatment sessions in the structured postoperative physiotherapy group reported less neck pain frequency (p = 0.05), and greater expectation fulfilment (p = 0.001), and enablement (p = 0.04) than those who received standard postoperative approach. These patients also had larger improvements in neck functioning, arm pain and catastrophizing during the rehabilitation period from 3 to 6 months after surgery (p< 0.03). Sixty-one percent of the patients who received standard postoperative approach reported additional use ofpostoperative physiotherapy. These patients had a worse surgical outcome compared with patients who reported no additional use of postoperative physiotherapy. In patients with CR who were scheduled for surgery, larger errors in head repositioning accuracy were found compared to neck-healthy individuals (Paper I). Preoperative measures of neck-related body functions, mental functions and other contextual factors explained 73% of the variance in Neck Disability Index scores in patients with CR who were scheduled for surgery (Paper II).The results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery. However, CR is a heterogeneous condition and specific subgroups of patients are likely to benefit from different interventions. More studies are needed to inform evidence-based clinical guidelines for the treatment of patients with CR. A broader preoperative assessment in patients with CR improved the description of patient-reported neck disability.
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