Rejected

To guide clinicians in balancing the risks and benefits of opioids when treating pain, we conducted two systematic reviews: 1) the impact of pain on cognitive function, and 2) the impact of opioids on cognitive function.

Postdural puncture headache (PDPH) is a complication associated with spinal and epidural anesthesia, characterized by a very severe dull, non-throbbing positional headache along with nausea, vomiting and other symptoms. The aim of this study was to compare positional character of PDPH, where the effects of prone and supine positions during surgery were compared for the risk of the headache.

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding of participants consulting healthcare due to mental illness or pain during follow-up. Regarding of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745).

Suicide is the second leading cause of death in young adults. Suicide attempts by violent methods predict later completed suicide and premature mortality. Suicide prevention is a major public health issue in this specific population. The French Student Health Foundation (FSEF) developed a psychiatric ward that includes psychiatric and somatic approaches. This transdisciplinary unit provides mixed psychiatric and rehabilitation treatments for those persons who have attempted suicide and have severe somatic injuries.

Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as "COVID-19" with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, "brain fog," insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named "LONG COVID." Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in "LONG COVID" subjects experiencing insomnia, depression, fatigue, and "brain fog" but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.

Cancer patients may have a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal secretion of cortisol. Increased cortisol levels have been associated with worse prognosis in patients with different types of tumors. Although anxiety and depression can trigger an abnormal cortisol secretion, little is known regarding the influence of these emotional disorders on HPA axis dysregulation in cancer patients when evaluating together with demographic, clinicopathological and biobehavioral variables. This cross-sectional study analyzed the pre-treatment plasma cortisol levels of 133 patients with oral squamous cell carcinoma (OSCC) and its association with demographic, clinicopathological, biobehavioral and psychological variables. Plasma cortisol levels were measured by electrochemiluminescence, and anxiety and depression symptoms were assessed using Beck Anxiety Inventory (BAI) and Depression (BDI), respectively. Demographic, clinicopathological and biobehavioral data were collected from patients' medical records. Results from multivariate analysis showed that the occurrence of cancer-induced pain was predictive for higher cortisol levels (OR = 5.388, p = 0.003). Men with OSCC were 4.5 times more likely to have higher plasma cortisol levels than women (OR = 4.472, p = 0.018). The effect of sex on cortisol concentrations was lost in the adjusted model for clinical staging (OR = 2.945, p = 0.116). The absence of chronic alcohol consumption history was a protective factor for highest hormone concentrations in oral cancer patients (OR = 0.104, p = 0.004). Anxiety symptoms measured by BAI as "hands trembling" (OR = 0.192, p = 0.016) and being "nervous" (OR = 0.207, p = 0.0004) were associated with lower cortisol levels. In contrast, the feeling of "fear of losing control" was a risk factor for highest hormone concentrations (OR = 6.508, p = 0.0004). The global score and specific symptoms of depression measured by the BDI were not predictive for plasma hormone levels (p > 0.05). Together, our results show that pain, alcohol consumption and feeling fear are independent factors for increased systemic cortisol levels in patients with oral cancer. Therefore, psychological intervention, as well as control of pain and alcohol consumption, should be considered to prevent the negative effects of cortisol secretion dysregulation in cancer patients.

Fibromyalgia and depression are frequently comorbid. We propose a hormonal system model in understanding the underlying endogenous opioid system dysregulation in fibromyalgia with the utilization of the cold pressor test (CPT) in clinical practice to monitor treatment response to low-dose naltrexone (LDN) and the subsequent remission of major depressive disorder by restoring opioid tone. A 60-year-old professional on permanent disability presented with refractory depression and chronic widespread pain after years of multiple failed medication trials. Rating scales confirmed severe depression, Hamilton Rating Scale for Depression (HAM-D) of 20, a short cold pressor test (CPT) time of 21 seconds, and a face pain scale (FPS) of 8/10. Physical examination assessing for fibromyalgia was diagnostic, with 18/18 positive tender points. LDN, a minor increase in trazodone, and transference-focused psychotherapy were employed. The patient's CPT time increased modestly. The patient achieved remission of both conditions in 10 weeks when both disorders were treated at once (FPS and HAM-D of zero), restoring the quality of life, relatedness, and motivation. Some fibromyalgia patients may achieve remission of comorbid depression with concomitant low-dose naltrexone (LDN) treatment that is widely used "off label" to treat pain. LDN is a promising alternative for the treatment of chronic pain in fibromyalgia with its safety profile, high tolerability, and absence of abuse potential. Our unique finding is that without successful LDN treatment of fibromyalgia, remission of depression may be unlikely.

Managing pain after thoracic surgery is crucial and the traditional methods have many adverse effects. We aimed to evaluate serratus anterior plane block (SAPB) and erector spinae plane block (ESPB) in acute pain control in thoracic cancer surgeries.

Background Anal fistula, or fistula-in-ano, is a chronic abnormal communication between the epithelialized surface of the anal canal and the perianal skin. Video-assisted anal fistula treatment (VAAFT) is a novel, minimally invasive, and sphincter-saving alternative to traditional seton use. This study aimed to determine the short-term and long-term outcomes of VAAFT compared with seton treatment. Material and methods This randomized control trial was conducted at the Department of Surgery, Services Hospital, Lahore, from August 2014 to July 2020. Patients were randomly assigned to either the VAAFT group or the seton group, and postoperative outcomes were assessed for up to three years. Results The study included 80 patients (64 men and 16 women) with a mean age of 39.1 ± 11.2 years. The most common type of fistula was a transsphincteric fistula (n=36, 45%). The mean duration of surgery was significantly longer in the VAAFT group (78.6 minutes) compared with the seton group (36.97 minutes; p=0.000). The mean pain score was significantly higher in the VAAFT group (4.22) compared to the seton group (2.82, p=0.000). The mean time to return to work was shorter in the VAAFT group (7.4 days) than in the seton group (9.2 days, p=0.000). The mean healing time was significantly shorter for patients treated with VAAFT (5.75 weeks) than for those treated with a seton (9.7 weeks; p=0.000). Fistula recurrence after one, two, or three years was not significantly different between groups, and neither group had incidences of anal incontinence. Conclusions VAAFT is associated with earlier healing time and earlier return to work than the traditional seton technique, with no significant difference in fistula recurrence. VAAFT is minimally invasive and, when used in patients where indicated, allows for a prompter return to routine life for the patients, which is an optimal outcome for both patients and physicians.

Programmed death-1 (PD-1) inhibitors have been approved and are currently widely used to treat lung cancer patients. However, comparative data on the adverse events (AEs) associated with different PD-1 inhibitors are very limited.