Obesity is a major public health problem. Bariatric surgery is currently the only available treatment that offers sufficient weight-loss and metabolic benefits over time. Although bariatric surgery is considered safe now, serious complications still occur. The aim of this thesis was to identify factors associated with an increased risk for postoperative complication after laparoscopic gastric bypass surgery. Study I included patients operated with laparoscopic gastric bypass surgery in Sweden from May 2007 until September 2012. The risk for serious complication was low (3.4%). Suffering an intraoperative adverse event or conversion of the operation to open surgery were the strongest risk factors for postoperative complication. The annual operative volume and experience of the procedure at the institution were also important risk factors. Patient-specific risk factors appeared to be less important although age was associated with an increased risk. In Study II, a raised glycated haemoglobin A1c (HbA1c) was evaluated as a risk factor for serious postoperative complications in non-diabetics. A higher incidence of serious postoperative complications was seen with elevated HbA1c values, even at levels classified as ‘‘pre-diabetic’’. Study III was a multicentre, randomised clinical trial (RCT). 2507 patients planned for laparoscopic gastric bypass surgery were randomised to either mesenteric defects closure or non-closure. Closure of the mesenteric defects reduced the rate of reoperation for small bowel obstruction from 10.2% to 5.5% at 3 years after surgery. A small increase in the rate of serious postoperative complication within the first 30 days was seen with mesenteric defects closure. This relatively small increase in risk was however outweighed by the marked reduction of later reoperations for small bowel obstruction. Study IV was a comparison between study III and an observational study on the same population under the same period of time. Although the observational study reached the same conlusion as the RCT, the efficacy of mesenteric defects closure was less pronounced. Observational studies may thus be an alternative to RCTs under situations when RCTs are not feasible. The efficacy may however be underestimated.

Abdominal aortic aneurysm (AAA) is a common disease that develops gradually over several years and is characterised by weakening and dilatation of the aortic wall. AAAs also demonstrates a marked inflammatory infiltrate throughout the aortic wall. Chlamydophila pneumoniae (C. pneumoniae), is a common bacterium. About 50% of the population has been infected in adolescence. Thirteen studies report the presence of either C. pneumoniae or its antigens in 35-100% of AAA specimens. The overall aim of this thesis was to evaluate the possible role of C. pneumoniae in inflammatory response and expansion of AAA from a clinical point of view. In paper I, viable C. pneumoniae was detected in a majority of 26 patients with AAA having open surgery. Patients operated for AAA had higher C. pneumoniae antibodies titers than controls. In paper II, 247 patients were randomised in a double-blind trial, to evaluate the effect of azithromycin on the expansion of small AAAs. No such effect was seen and there was no correlation between C. pneumoniae antibody titers and AAA expansion. In paper III, 42 patients with AAA were compared to 100 age- and sex matched controls with normal aortas. C. pneumoniae antibodies were analysed in plasma samples obtained at screening, and in samples from a study conducted 5-15 (mean 12) years previously on the same population. There was no significant difference between the groups. In paper IV, were 211 patients were analysed, we could not find an association between levels in plasma of three markers of inflammation (IL-6, MMP-9 and CRP) and AAA expansion. A significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins. In conclusion, viable C. pneumoniae is found at the scene of the crime, but we were unable to reverse or halt expansion of AAA with antibiotic treatment. C. pneumoniae antibody titers cannot be used, to detect small AAA, or to evaluate AAA expansion. From a clinical point of view, based on the methods and analyses used in this thesis, the role of C. pneumoniae in the inflammatory response and expansion of abdominal aortic aneurysms is limited.

Objetivo: Avaliar a eficácia da fisioterapia respiratória como tratamento adjuvante em pacientes pediátricos com pneumonia adquirida na comunidade. Delineamento: Ensaio clínico randomizado Local do estudo: Hospital da Criança Santo Antônio – Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Participantes e métodos: Foram arroladas crianças com idade entre 1 e 12 anos, com diagnóstico clínico e radiológico confirmado de pneumonia, hospitalizadas no período de setembro de 2001 a setembro de 2002. Os pacientes que preencheram os critérios de inclusão foram randomizados para receber fisioterapia respiratória três vezes ao dia (grupo intervenção) ou para receber, uma vez ao dia, orientações para respirar profundamente, expectorar a secreção e manter preferencialmente o decúbito lateral (grupo controle). As variáveis analisadas na linha de base, no primeiro e no segundo períodos de seguimento e no dia da alta hospitalar foram: escore de gravidade (composto pela freqüência respiratória anormal para a idade, tiragem supra-esternal, intercostal, e subcostal, febre, saturação de oxigênio da hemoglobina e raio-x de tórax), duração da hospitalização, freqüência respiratória, temperatura e saturação do oxigênio. Resultados: Setenta e dois pacientes foram randomizados para os grupos intervenção ou controle. Destes, sete foram retirados devido a complicações como atelectasia ou drenagem pleural. Dentre os 65 pacientes estudados no primeiro seguimento (terceiro dia), a febre foi mais prevalente no grupo intervenção (34,4%) do que no grupo controle (12,5%), bem como o escore de gravidade 9,63 ± 1,62 e 8,71 ± 0,86 pontos, respectivamente. No segundo seguimento, entre o quarto e sexto dia, a diferença entre os grupos teve tendência à significância apenas para febre, 31,6% no grupo intervenção e 6,7% no grupo controle (P= 0,07). A duração média da hospitalização foi de 7,41 ± 6,58 dias para o grupo intervenção e 4,52 ± 2,21 dias para o controle. Conclusão: Neste ensaio clínico, a fisioterapia prolongou a hospitalização e a duração da febre nos pacientes pediátricos com pneumonia adquirida na comunidade. Nestes pacientes, a fisioterapia é prejudicial e não deveria ser prescrita até que evidências de benefício estejam disponíveis. / Objective: To evaluate the efficacy of chest physiotherapy as a supplementary treatment in paediatric patients hospitalised with acute community-acquired pneumonia. Study design: a randomised clinical trial. Setting: Hospital da Criança Santo Antônio, Complexo Hospitalar Santa Casa, Porto Alegre, RS, Brasil. Patients and Methods: Children between 1 and 12 years of age, with confirmed clinical and radiological diagnosis of pneumonia, hospitalised between September 2001 and September 2002 were eligible to the trial. Participants were selected at random to receive respiratory physiotherapy three times daily (intervention group) or to receive once a day orientation to breath deeply, expectorate the sputum and to maintain preferably a lateral body position (control group). The variables analysed at the baseline, the first and second follow-up periods, and at hospital discharge were (1) the severity score (composed of age, respiratory rate, suprasternal, intercostal and subcostal retractions, fever, saturation of the haemoglobin oxygen and thorax x-rays), (2) the duration of hospitalisation, (3) respiratory rate, and (4) temperature. Results: Seventy-two patients were divided randomly into the intervention and control groups. Of these, seven were subsequently withdraw of the study due to complications such as atelectasis at the x-ray or pleural drainage. Amongst the 65 patients examined on the first follow-up (on the third day) fever was more prevalent in the intervention group (34.4%) than in the control group (12.5%) and the severity score showed the same tendency (9.63 ±1.62 and 8.71 ±0.86 points, respectively). At the second follow-up assessment, between the fourth and sixth day, the differences between the groups had a borderline statistical significance for fever (31.6% for the intervention group and 6.7% for the control group; P= 0.07). The average length of hospitalisation was 7.41 ±6.58 days for the intervention group and 4.52 ±2.21 days for the control. Conclusion: In this clinical trial, physiotherapy increased the hospital stay and the duration of fever in patients with acute pneumonia acquired in the community. In such patients physiotherapy may be prejudicial and should not be prescribed until evidence of benefit is available.

Objetivo: Avaliar a eficácia da fisioterapia respiratória como tratamento adjuvante em pacientes pediátricos com pneumonia adquirida na comunidade. Delineamento: Ensaio clínico randomizado Local do estudo: Hospital da Criança Santo Antônio – Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Participantes e métodos: Foram arroladas crianças com idade entre 1 e 12 anos, com diagnóstico clínico e radiológico confirmado de pneumonia, hospitalizadas no período de setembro de 2001 a setembro de 2002. Os pacientes que preencheram os critérios de inclusão foram randomizados para receber fisioterapia respiratória três vezes ao dia (grupo intervenção) ou para receber, uma vez ao dia, orientações para respirar profundamente, expectorar a secreção e manter preferencialmente o decúbito lateral (grupo controle). As variáveis analisadas na linha de base, no primeiro e no segundo períodos de seguimento e no dia da alta hospitalar foram: escore de gravidade (composto pela freqüência respiratória anormal para a idade, tiragem supra-esternal, intercostal, e subcostal, febre, saturação de oxigênio da hemoglobina e raio-x de tórax), duração da hospitalização, freqüência respiratória, temperatura e saturação do oxigênio. Resultados: Setenta e dois pacientes foram randomizados para os grupos intervenção ou controle. Destes, sete foram retirados devido a complicações como atelectasia ou drenagem pleural. Dentre os 65 pacientes estudados no primeiro seguimento (terceiro dia), a febre foi mais prevalente no grupo intervenção (34,4%) do que no grupo controle (12,5%), bem como o escore de gravidade 9,63 ± 1,62 e 8,71 ± 0,86 pontos, respectivamente. No segundo seguimento, entre o quarto e sexto dia, a diferença entre os grupos teve tendência à significância apenas para febre, 31,6% no grupo intervenção e 6,7% no grupo controle (P= 0,07). A duração média da hospitalização foi de 7,41 ± 6,58 dias para o grupo intervenção e 4,52 ± 2,21 dias para o controle. Conclusão: Neste ensaio clínico, a fisioterapia prolongou a hospitalização e a duração da febre nos pacientes pediátricos com pneumonia adquirida na comunidade. Nestes pacientes, a fisioterapia é prejudicial e não deveria ser prescrita até que evidências de benefício estejam disponíveis. / Objective: To evaluate the efficacy of chest physiotherapy as a supplementary treatment in paediatric patients hospitalised with acute community-acquired pneumonia. Study design: a randomised clinical trial. Setting: Hospital da Criança Santo Antônio, Complexo Hospitalar Santa Casa, Porto Alegre, RS, Brasil. Patients and Methods: Children between 1 and 12 years of age, with confirmed clinical and radiological diagnosis of pneumonia, hospitalised between September 2001 and September 2002 were eligible to the trial. Participants were selected at random to receive respiratory physiotherapy three times daily (intervention group) or to receive once a day orientation to breath deeply, expectorate the sputum and to maintain preferably a lateral body position (control group). The variables analysed at the baseline, the first and second follow-up periods, and at hospital discharge were (1) the severity score (composed of age, respiratory rate, suprasternal, intercostal and subcostal retractions, fever, saturation of the haemoglobin oxygen and thorax x-rays), (2) the duration of hospitalisation, (3) respiratory rate, and (4) temperature. Results: Seventy-two patients were divided randomly into the intervention and control groups. Of these, seven were subsequently withdraw of the study due to complications such as atelectasis at the x-ray or pleural drainage. Amongst the 65 patients examined on the first follow-up (on the third day) fever was more prevalent in the intervention group (34.4%) than in the control group (12.5%) and the severity score showed the same tendency (9.63 ±1.62 and 8.71 ±0.86 points, respectively). At the second follow-up assessment, between the fourth and sixth day, the differences between the groups had a borderline statistical significance for fever (31.6% for the intervention group and 6.7% for the control group; P= 0.07). The average length of hospitalisation was 7.41 ±6.58 days for the intervention group and 4.52 ±2.21 days for the control. Conclusion: In this clinical trial, physiotherapy increased the hospital stay and the duration of fever in patients with acute pneumonia acquired in the community. In such patients physiotherapy may be prejudicial and should not be prescribed until evidence of benefit is available.

Objetivo: Avaliar a eficácia da fisioterapia respiratória como tratamento adjuvante em pacientes pediátricos com pneumonia adquirida na comunidade. Delineamento: Ensaio clínico randomizado Local do estudo: Hospital da Criança Santo Antônio – Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Participantes e métodos: Foram arroladas crianças com idade entre 1 e 12 anos, com diagnóstico clínico e radiológico confirmado de pneumonia, hospitalizadas no período de setembro de 2001 a setembro de 2002. Os pacientes que preencheram os critérios de inclusão foram randomizados para receber fisioterapia respiratória três vezes ao dia (grupo intervenção) ou para receber, uma vez ao dia, orientações para respirar profundamente, expectorar a secreção e manter preferencialmente o decúbito lateral (grupo controle). As variáveis analisadas na linha de base, no primeiro e no segundo períodos de seguimento e no dia da alta hospitalar foram: escore de gravidade (composto pela freqüência respiratória anormal para a idade, tiragem supra-esternal, intercostal, e subcostal, febre, saturação de oxigênio da hemoglobina e raio-x de tórax), duração da hospitalização, freqüência respiratória, temperatura e saturação do oxigênio. Resultados: Setenta e dois pacientes foram randomizados para os grupos intervenção ou controle. Destes, sete foram retirados devido a complicações como atelectasia ou drenagem pleural. Dentre os 65 pacientes estudados no primeiro seguimento (terceiro dia), a febre foi mais prevalente no grupo intervenção (34,4%) do que no grupo controle (12,5%), bem como o escore de gravidade 9,63 ± 1,62 e 8,71 ± 0,86 pontos, respectivamente. No segundo seguimento, entre o quarto e sexto dia, a diferença entre os grupos teve tendência à significância apenas para febre, 31,6% no grupo intervenção e 6,7% no grupo controle (P= 0,07). A duração média da hospitalização foi de 7,41 ± 6,58 dias para o grupo intervenção e 4,52 ± 2,21 dias para o controle. Conclusão: Neste ensaio clínico, a fisioterapia prolongou a hospitalização e a duração da febre nos pacientes pediátricos com pneumonia adquirida na comunidade. Nestes pacientes, a fisioterapia é prejudicial e não deveria ser prescrita até que evidências de benefício estejam disponíveis. / Objective: To evaluate the efficacy of chest physiotherapy as a supplementary treatment in paediatric patients hospitalised with acute community-acquired pneumonia. Study design: a randomised clinical trial. Setting: Hospital da Criança Santo Antônio, Complexo Hospitalar Santa Casa, Porto Alegre, RS, Brasil. Patients and Methods: Children between 1 and 12 years of age, with confirmed clinical and radiological diagnosis of pneumonia, hospitalised between September 2001 and September 2002 were eligible to the trial. Participants were selected at random to receive respiratory physiotherapy three times daily (intervention group) or to receive once a day orientation to breath deeply, expectorate the sputum and to maintain preferably a lateral body position (control group). The variables analysed at the baseline, the first and second follow-up periods, and at hospital discharge were (1) the severity score (composed of age, respiratory rate, suprasternal, intercostal and subcostal retractions, fever, saturation of the haemoglobin oxygen and thorax x-rays), (2) the duration of hospitalisation, (3) respiratory rate, and (4) temperature. Results: Seventy-two patients were divided randomly into the intervention and control groups. Of these, seven were subsequently withdraw of the study due to complications such as atelectasis at the x-ray or pleural drainage. Amongst the 65 patients examined on the first follow-up (on the third day) fever was more prevalent in the intervention group (34.4%) than in the control group (12.5%) and the severity score showed the same tendency (9.63 ±1.62 and 8.71 ±0.86 points, respectively). At the second follow-up assessment, between the fourth and sixth day, the differences between the groups had a borderline statistical significance for fever (31.6% for the intervention group and 6.7% for the control group; P= 0.07). The average length of hospitalisation was 7.41 ±6.58 days for the intervention group and 4.52 ±2.21 days for the control. Conclusion: In this clinical trial, physiotherapy increased the hospital stay and the duration of fever in patients with acute pneumonia acquired in the community. In such patients physiotherapy may be prejudicial and should not be prescribed until evidence of benefit is available.

Anterior knee pain (AKP) is a common, chronic lower limb musculoskeletal overuse condition that represents substantial morbidity to those affected, and has a significant impact on the health care industry. Health practitioners frequently prescribe foot orthoses in the management of AKP as an alternative or adjunct to multimodal physiotherapy. The primary aim of this thesis was to investigate the clinical efficacy of foot orthoses in AKP, utilising high-quality research methodologies. The two systematic reviews conducted have identified a significant gap in the literature regarding evidence from randomised clinical trials (RCTs) for foot orthoses in AKP and other lower limb overuse conditions. While the best evidence for AKP management was for multimodal physiotherapy, there was insufficient evidence to support or refute the use of foot orthoses in the treatment of lower limb overuse conditions, including AKP. Meta-analysis provided evidence to support the use of foot orthoses in the prevention of the first incidence of lower limb overuse conditions. An interesting finding was evidence from pooled and individual study data of no difference between custom and prefabricated foot orthoses in both treatment and prevention of lower limb overuse conditions, inferring that either type of orthosis may be utilised. Both systematic reviews highlighted substantial methodological flaws of the included studies, and recommended that future studies include larger participant numbers, longer participant follow-up, more consistent use of reliable and valid outcome measures and reporting of outcome data, and utilisation of the CONSORT guidelines in the design and reporting of RCTs. A 12-month prospective RCT investigated the short- and long-term clinical efficacy of prefabricated foot orthoses in the treatment of 179 participants with AKP. Foot orthoses were more effective than flat shoe inserts in the short term, implying that their contoured form has some therapeutic effect. Foot orthoses were not significantly different to multimodal physiotherapy over 12 months, nor was there any benefit in adding foot orthoses to physiotherapy. Considering that all groups experienced clinically meaningful long-term improvements in pain and function, clinicians may prescribe foot orthoses for AKP to hasten recovery. Findings of post-hoc analyses to develop a clinical prediction rule indicate that those of older age and shorter height, who have a lower severity of AKP and a more mobile midfoot, are more than twice as likely to experience a successful outcome with foot orthoses. As a secondary aim, this thesis has provided a more comprehensive profile of AKP as a condition. Baseline data from the RCT participants confirms previous reports of higher rates of AKP in females, and a tendency towards bilaterality and chronicity. This AKP sample did not differ from asymptomatic individuals in terms of body mass index, physical activity level, general and mental health, and foot posture, although they tended to have a more mobile foot under load. These characteristics tend to be homogenous across a number of published RCTs, indicating that the findings of the RCT described above are likely to be generalisable to the broader population with AKP. An additional finding in this group was that those with AKP of long duration, higher pain levels, lower functional levels, and an overall lower score on a specific measure of AKP have a poorer prognosis over 12 months, irrespective of their age, gender or morphometry. These findings suggest that, in order to improve prognosis and the chance of a successful outcome, the primary goals of intervention should be to reduce the severity and duration of AKP, through the use of early intervention with foot orthoses, multimodal physiotherapy, or a combination of the two.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.