Meniscal tears are amongst the most common knee injuries. The purpose of the current article is to identify the most common meniscal tears, current treatment options, and potential future treatment methods. The traditional approach to meniscal tears was total meniscectomy. However, this approach has been largely abandoned due to the emergent relationship between even partial meniscectomy and the early onset and development of osteoarthritis. Complete meniscectomy is indicated only if the meniscus is torn beyond repair, however, preservation of the meniscal rim is always a priority. Tears in the peripheral one-third region are well suited for repair and these have high success rates. When irreparable damage is encountered, removal and replacement of the meniscus with natural or synthetic scaffolds presents a promising option if its efficacy can be definitively demonstrated in future trials.

Introduction

The menisci are a pair of semilunar, wedge-shaped fibrocartilaginous structures sitting between the femur and the tibia within the tibiofemoral joint of each knee. They are involved in load transmission and produce significant load-spreading across the articular surfaces in normal knees [1,2], as well as shock-absorption, which is reduced in painful knees [3]. Other meniscal functions include joint lubrication [4], structural stability [5], and proprioception [6].

Meniscal tears are among the most common knee injuries and can be secondary to trauma or degenerative changes [7]. The former occurs when excessive force is applied to a normal meniscus while the latter occurs from normal forces acting on a degenerative structure [8]. Acute tears are usually caused by a traumatic, twisting motion of the knee, frequently during sports [7]. Sports-related meniscal tears are often associated with anterior cruciate ligament (ACL) rupture [7,9].

In addition to the two aetiological categories mentioned, meniscal tears can be classified according to the pattern of rupture seen at arthroscopy [8]. The most commonly described patterns of meniscal injury are as follows:

• Horizontal (cleavage) tears: These tears result from shear stresses generated by inferior and superior sections of the meniscus, causing the meniscus to cleave into two layers [7,8]. Horizontal tears are difficult to manage and are not usually amenable to repair.
• Vertical (longitudinal/circumferential) tears (Figure 1): These are the most common type of meniscal tear to be repaired. They can vary in size between ~1mm to the full length of the meniscus [8]. The Bucket-handle tear (Figure 2) is a type of vertical longitudinal tear in which the inner margin is displaced from the remainder of the meniscus. Depending on the extent of injury, it can be unstable and cause mechanical symptoms such as the classical “lock knee” [8]. Owing to its more secure attachment to the tibial plateau, the medial meniscus is more prone to shear forces and is more commonly affected [8].

Figure 1: Peripheral longitudinal tear. Source: Dr Andrew Stuart

Figure 2: Bucket-handle tear. Source: Dr Andrew Stuart

• Oblique (flap/parrot-beak) tears (Figure 3): These are tears that proceed towards the periphery at an acute angle to the meniscal margin. Oblique tears can occur at any point along the meniscus but most often between the posterior- and middle-thirds of the meniscus. Propagation of the tear or mechanical symptoms can be elicited by a free flap catching in the articular interface [8]. Along with vertical tears, they make up 81% of all tears [8].

Figure 3: Oblique (flap) tear. Source: Dr Andrew Stuart

• Radial (transverse) tears: These are tears that occur across the circumferential fibers of the meniscus (Figure 4). They are commonly seen following ACL disruption. Radial tears may extend to the periphery if not treated, at which point they disrupt the natural hoop stresses of the meniscus and interfere with its natural load-spreading and shock-absorptive functions [8].

Figure 4: Types of meniscal tears. Source: Hope Orthopaedics

• Complex tears: These are degenerative in nature, composed of several different tears in multiple planes resulting from persistent hoop and sheer stresses, and are often associated with degeneration of articular cartilage [10]. Together, they feature in the pathology of degenerative arthritis, which is positively associated with older age [8,11]. The healing potential of chronic degenerative menisci remains poor and conservative treatment is recommended except in refractory cases [10].

Methods

A literature search of publications relating to meniscal repairs was undertaken. The databases PubMed, CINAHL, and Ovid were searched. The search terms “Meniscus OR Meniscal”, “Tear”, “Treatment OR Repair OR Surgery”, “Knee”, “Options” and “Outcome” were used. This search yielded 453 publications. Additional articles were obtained from bibliographic screening. After the search, articles that were not relevant to meniscal tears of the knee and treatment options were excluded. In the final analysis, 37 articles were included in the current review.

Meniscectomy

The traditional approach to meniscal tears, until the 1970s, was total meniscectomy [11]. However, this approach has been largely abandoned due to the emergent relationship between even partial meniscectomy and the early onset and development of osteoarthritis (OA) [7,12-15]. Meniscectomies have been shown to cause joint-space narrowing, lowering the rate of regeneration, leading to an increase in the degenerative changes in the surrounding cartilage, and hence a higher incidence of OA [16-20]. In a normal knee, the menisci transmit 50% of joint-compressive forces in full extension and 85% of the load at 90° of flexion [21]. However, following a total meniscectomy, the tibiofemoral contact area is reduced by approximately 75%, while contact forces increase by 235% [1,2]. Today, repair and preservation of the menisci is the universally-accepted approach to meniscal tears.

Untreated meniscal damage is a potent risk factor for the development of OA [22]. When meniscal repair is not possible, partial meniscal resection is preferred to total meniscectomy, and is associated with less radiographic OA over time [22,23]. A systematic review of clinical outcomes found lateral meniscectomy to be associated with significantly greater frequency of radiographic OA, reduced knee function and future instability than medial meniscectomy [24]. The lateral meniscus has been reported to carry a higher load in the knee compared with the medial meniscus, and its loss may result in increased cartilage contact stress [22]. Furthermore, degenerative meniscal tear and cartilage changes at the time of surgery were associated with radiographic OA more frequently than were longitudinal tear and absence of cartilage changes, respectively [22].

Current treatment methods

Meniscus surgery procedures have rapidly developed from open procedures to arthroscopic surgery over the past two decades [25]. Reparability of the meniscus depends on several factors, such as vascularity, type of tear, chronicity, and size [15,26]. Complete meniscectomy is indicated only if the meniscus is torn beyond repair, however, preservation of the meniscal rim is always a priority [15,26,27].

The indications for meniscus repair include: active patients with tibiofemoral joint line pain, patients younger than 50, or patients between 50 and 60 who are athletically active. Repair may also be undertaken with concurrent knee-ligament reconstruction, a reducible meniscus tear, and good tissue integrity [28].

Tears in the peripheral one-third region (zone 1, also known as the red-red zone due to its high vascularity; Figure 5) are well suited for repair, and these have high success rates. Tears in the middle-third region (zone 2, also known as the red-white zone) are often reparable with reasonable success rates. Longitudinal, radial, and horizontal tears confined to zones 1 and 2 are patterns that are usually amenable to repair [28-30]. The vascularity of the menisci is important, as it is critical to the success of a healing response. Meniscal vascularity has been described by Arnoczky and Warren [31]. The degree of vascular penetration was found to be 10-30% of the width of the medial meniscus, and 10-25% of the width of the lateral meniscus. Therefore, tears in the vascular zone have the highest chance of healing. Cannon and Vittori [32] reported a decline in healing rates as tear location moved from peripheral to central: 90% for tears within 2 mm of the periphery, 74% for tears within 3 mm of the periphery and 50% for tears within 4-5 mm of the periphery. The length of the tear has also been suggested to affect repair outcome. Cannon and Vittori [32] reported 90% and 50% healing rates for tears less than 2 cm and greater than 4 cm, respectively. Bach et al. [33] documented significantly earlier failure in larger tears. However, other data has been unable to demonstrate a significant difference in repair outcomes based on tear length [33].

Figure 5: Types of meniscal tears. Source: Hope Orthopaedics

The identification of meniscal tears suitable for repair is usually made at the time of arthroscopy. The three general meniscal repair techniques are as follows:

• Inside-out repair technique: This technique uses sutures placed in the menisci from within the joint cavity and tied over the capsule through a limited open approach. This technique is the gold standard with which other repair techniques are compared [34,35]. However, comparable results are reported with other techniques that are less technically demanding [35].
• Outside-in repair technique: Sutures are introduced into the knee through the lumen of a standard spinal needle, where they are visualised by the arthroscope. The suture is then drawn through a portal and interference knot tied. The knot is pulled back into the knee where it tamps down the torn meniscal fragments. This technique is mostly suited to tears in the anterior and adjacent middle segments of the meniscus [36].
• All-inside repair technique: This is a more recent technique, favoured by most clinicians due to its lower complication rate and lower morbidity [37,38]. It can be divided into two types: one that uses resorbable, rigid arrows (darts and staples), which provide rigid fixation, and one that employs flexible, suture-based repair devices, which deploy anchors for stability [39]. These arrows and sutures are designed to hold the meniscal fragments together while healing occurs. They are popular, as they do not necessitate an additional skin incision. However, some of the rigid devices have demonstrated inferior mechanical properties compared with sutures [39-41]. Suture-based devices were developed in an attempt to avoid the complications associated with rigid devices and to allow a more flexible fixation of the meniscal fragments [42]. Success rates of 83-88% have been reported for this technique [43,44].

Arthroscopic trephination of vascular channels at the free meniscal edges has also shown improved meniscal healing. Trephination is a safe and easy procedure that involves the creation of a channel through the meniscus from the vascularised zone to the tear. Fox et al. [45] reported good results in 90% of cases and Zhang et al. [46,47] showed trephination led to healing of all tears, either partially or fully [47], with an improved healing rate and lower re-tear rate compared with suturing alone [46].

Not all meniscal tears can or should be repaired, particularly if considerable damage has been sustained. Contraindications include: tears located in the inner-third region (zone 3, also known as the white-white zone, where the tissue is entirely devoid of a vascular supply), and tears with major degeneration. Longitudinal tears measuring less than 10 mm in length and incomplete radial tears that do not extend into the outer one-third of the meniscus should also not be repaired. Older patients (above 60 years of age) and those unwilling to follow post-operative rehabilitation programs would also be unsuitable candidates [28].

Degenerative (complex) tears in older patients are among those tears historically treated by unnecessarily invasive means. Sihvonen et al. [48] conducted a randomised sham-controlled trial in patients with a degenerative meniscal tear and no knee OA. Patient outcomes after arthroscopic surgery were no better than those after a sham operation. A subsequent meta-analysis showed a small, clinically insignificant benefit from surgical intervention that is entirely absent within two years [49]. Current evidence does not support a role for arthroscopic debridement, washout, or partial meniscectomy for middle-aged and older patients with knee pain with or without signs of OA [49,50]. First-line treatment comprises non-operative modalities, such as education; self-management; exercise; weight loss, if overweight or obese; walking aids, if indicated, paracetamol; non-steroidal anti-inflammatory drugs; and intra-articular glucocorticoids [50]. Knee pain refractory to conservative therapy may respond to partial meniscectomy in the absence of OA when combined with a physiotherapy program, however, relief does not persist in the long-term [10].

Meniscus replacement

Potential future treatments have expanded their focus beyond the conventional methods. In some cases, there may be an indication to resect and replace the entire meniscus. Meniscal replacement has a greater capacity to protect the joint surfaces and is a suitable option in cases where patients have suffered degenerative changes due to prior meniscectomy or when an irreparable tear is encountered [16]. Meniscal replacement surgery uses natural or synthetic scaffolds to guide tissue repair or regeneration in three dimensions while providing a temporary construct for mechanical function [51]. Clinical application of both allograft transplantation and synthetic replacement scaffolds show promising results [52], however, their superiority to partial meniscectomy still needs to be demonstrated [53].

Conclusion

Meniscal tears are a common orthopaedic pathology that may have an acute traumatic or chronic degenerative cause. Due to the likely complication of OA, alternatives are now preferred to total meniscectomy. There are several surgical approaches suited to treating different patterns of meniscal tear. Where indicated, meniscal repair is the preferred method of treatment, with evidence supporting very good long-term results. When irreparable damage is encountered, removal and replacement of the meniscus with natural or synthetic scaffolds presents a promising option, provided its efficacy can be definitively demonstrated in future trials.

Acknowledgements

The authors wish to acknowledge Hope Orthopaedics for supplying Figure 4 and Figure 5.

Conflicts of interest

None declared.

Correspondence

K Wegrecki: kamil.wegrecki1@my.nd.edu.au

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Purpose of review: To determine the maternal and neonatal outcomes after operative vaginal delivery of foetuses in the persistent occiput posterior position, and examine the efficacy and outcomes of techniques to rotate the foetus into an occiput anterior position prior to vaginal delivery. Summary of findings: A literature search of the MEDLINE/PubMed databases was conducted to identify all study types examining the management of persistent occiput posterior position during labour and subsequent maternal and neonatal outcomes.

Maternal posturing in the last four weeks of pregnancy or during labour has no benefit in reducing the incidence of occiput posterior position at delivery. Rotational operative vaginal deliveries tend to have a low failure rate, however may be associated with anal sphincter injury, despite the overall risk being low. The most current evidence supports the use of rotational forceps in achieving a successful vaginal delivery. Manual rotation followed by direct traction forceps is a commonly performed method of delivery for the occiput posterior positioned foetus, however has only been directly compared to rotational forceps or vacuum in one study, with no demonstrable statistical difference in maternal or neonatal outcomes. Further evidence from the POP-OUT study currently in progress may further support an increasing role for manual rotation in the management of occiput posterior position at delivery.

Introduction

Occiput posterior (OP) describes the foetal head position where the base of the skull abuts the mother’s sacrum, and the forehead abuts the mother’s symphysis pubis. It is the most common foetal malpresentation and is of clinical important due to its associations with increased maternal and neonatal adverse outcomes. The management of the persistent OP position in labour continues to be an area of debate among obstetricians. Historically there has been conflicting opinion on the morbidity and mortality associated with the OP position. A number of early studies highlighted the increased incidence of operative deliveries and adverse maternal and neonatal outcomes [1, 2]. Interestingly, the basic principles for management of the OP position in labour remain largely unchanged into the modern era of obstetrics – conservative management in the first stage, and conflicting opinions in the second.

Recent studies suggest OP is the most common foetal malpresentation, with reported prevalence of 15-32% at the onset of labour and 5-8% at delivery [3, 4]. Approximately 90% of foetuses in the OP position at the onset of labour rotate into an anterior position without significant prolongation of labour [5]. Therefore the majority of OP positions at delivery arise through failure of rotation to the occiput anterior (OA) position during labour.

Maternal age greater than 35, nulliparity, or gestational age greater than 41 weeks at delivery have a higher incidence of OP position at delivery [4]. Studies have also shown an association between the use of epidural anaesthetic or oxytocin augmentation during labour, and increased rates of OP position at delivery [3]. Although not an established cause, studies have suggested inefficient uterine contractility during labour may account for a proportion of OP positions and may not always be correctible with oxytocin [6].

The OP position is associated with a number of adverse maternal outcomes including increased length of labour, augmentation of labour, chorioamnionitis, anal sphincter injury, and post-partum haemorrhage. Adverse outcomes to the neonate include lower 5-minute Apgar scores, cord blood acidosis, birth trauma, admission to neonatal intensive care units (NICU), and longer duration of stay in hospital [3, 4].

The increased rate of operative deliveries in the persistent OP position is similarly well documented. Studies suggest less than half the number of spontaneous vaginal deliveries occur in OP compared to OA. Furthermore, OP accounts for a disproportionate amount of assisted vaginal deliveries and caesarean sections [6].

Fetal head position has traditionally been determined by digital vaginal examination, by palpating the fontanelles and suture of the foetal skull. However, this has become problematic, as recent evidence suggests that vaginal examination fails to correctly determine the position of the foetal head in 72% of cases in the first stage, and 64% in the second [7]. This finding directly impacts the principles of management, as the exact position of the foetal head should be determined prior to any operative vaginal delivery to ensure safe and correct positioning of the instrument and a successful outcome. Furthermore, this brings into question the reliability of a number of studies in which the diagnosis of OP position was made with digital vaginal examination alone, as there is likely to be a large margin of error. Intrapartum ultrasonography continues to be an operator-dependent method that does not establish the exact position of the foetal head, however a recent study has shown promising results using an algorithm for quantitatively evaluating the position of the foetal head in the maternal pelvis [8]. Advances in ultrasonography techniques will likely continue to improve the utility of this technique, aiding clinicians in deciding whether or not to allow a vaginal delivery. More recent studies, such as the POP-OUT study, are implementing the routine use of transabdominal ultrasound early in the second stage of labour to reliably establish the diagnosis of OP position [9].

A number of large retrospective population based studies have examined the maternal and neonatal outcomes of instrumental vaginal deliveries, however there is limited data comparing the use of forceps and vacuum in the persistent OP position [10]. Furthermore, evidence is lacking for the effectiveness of these techniques in rotating the foetal head to an anterior position to improve outcomes during vaginal delivery.

This review aims to examine the current literature on maternal and neonatal outcomes after instrumental vaginal delivery of foetuses in the persistent OP position, as well as to examine the efficacy and outcomes of techniques to rotate the foetus into the OA position prior to vaginal delivery.

Methods

The criteria outlined below were used for consideration of studies to be included in this review.

Types of studies

All published studies of any type including randomised controlled trials, retrospective and prospective cohort studies, retrospective and prospective case-control studies, case series and systematic reviews, examining the management of persistent OP position during labour and subsequent maternal and neonatal outcomes were included.

Types of interventions

The interventions of interest were maternal posturing, operative vaginal delivery including forceps and vacuum, and manual rotation.

Types of outcomes

The primary maternal outcomes to be assessed were the occurrence of anal sphincter injury and postpartum haemorrhage.

The primary neonatal outcomes to be assessed were the occurrence of birth trauma, shoulder dystocia, 5-minute Apgar scores <7, and NICU admission.

For the purposes of this review, only the above short-term outcomes were assessed. However, it should be noted that there are a number of important longer-term outcomes that can be used to assess maternal morbidity. These include bowel and bladder dysfunction and haemorrhoids, which tend to occur more commonly in operative vaginal deliveries, as well as an increased risk of pelvic organ prolapse [11-13]. Recent evidence in this area suggests vacuum extraction shares a comparable risk of pelvic organ prolapse to spontaneous vaginal deliveries, however further discussion is outside the scope of this review [14]. Long-term sequelae of neonatal injury during operative vaginal deliveries appear to be uncommon [15].

Search strategy

An electronic keyword search of the MEDLINE/PubMed databases was conducted to identify studies according to the criteria above. The keywords labor, labour, and occiput posterior were used initially and combined as appropriate with rotation, rotational, operative, instrumental, forceps, vacuum, vaginal delivery using the Boolean operators AND and OR. The reference lists of review articles and other retrieved articles were also searched for relevant studies. The language was restricted to English. All studies up to the 1^st of November 2015 were included in the search strategy.

Selection of studies

The author assessed all potential studies identified as a result of the search strategy for inclusion. Only articles with full electronic text available were included in the analysis. To be included in the analysis studies needed to examine at least one maternal or neonatal outcome for an intervention of interest.

Results

A total of 198 studies were identified in the initial electronic search. 123 studies were available with full electronic text in English. 16 studies were screened for inclusion. An additional 8 studies were identified through reference lists and additional electronic searching. 14 studies were included for the final analysis based on the inclusion criteria above (Table 1). Articles were identified for all interventions to be examined. The majority of the included studies were retrospective cohort or population studies.

Table 1: Articles identified from the search strategy

RCT – Randomized control trial; ReCS – Retrospective cohort study; PCS – Prospective cohort study; ReCCS – Retrospective case-control study; SR – Systematic review

Discussion

Maternal positioning

A number of studies have examined the effect of maternal posturing and pelvic rocking exercises as an intervention for malposition of the foetus, however substantive evidence has been lacking. One study investigated the effect of ten minutes of hands and knees positioning with slow pelvic rocking beginning in the 37th week of gestation and continuing to the time of labour, as a prophylactic intervention to reduce the incidence of foetal malposition [16]. This large, multi-centre randomised controlled trial showed no difference in the incidence of persistent OP position at delivery. In this study foetal position was determined through ultrasonography at the onset of labour. Persistent OP accounted for 32% of all OP neonates at delivery, with the remaining likely to have come about through malrotation, consistent with the literature. This suggests maternal posturing before the start of labour would be of no benefit.

This was further explored in another randomised controlled trial where the intervention group were randomised at the onset of labour after ultrasonography confirmation of the foetal head in the OP position [17]. This study found that intervention with three different maternal postures corresponding to various stages of descent of the foetal head into the maternal pelvis had no significant effect on the foetal head rotation to the anterior position.

Non-rotational operative vaginal delivery

Several studies were identified examining maternal and neonatal outcomes in operative vaginal deliveries, however in two of these the data was not separated for OP position and will therefore not be discussed in detail. Briefly, Demissie and colleagues [18] found vacuum deliveries resulted in a lower risk of birth injuries, neonatal seizures, and anal sphincter injury. However in this study, rates of shoulder dystocia and postpartum haemorrhage were higher for vacuum deliveries. This study was limited by the data being sourced from birth certificates and administrative data, however the large sample size provided sufficient power to detect important differences in outcomes. In a smaller retrospective cohort study, the investigators showed vacuum deliveries resulted in less episiotomies (81.8% vs. 90.5%, p = 0.01), and a lower incidence of anal sphincter injury (27.9% vs. 44.4%, p < 0.001) [19]. Interestingly, more periurethral tears were seen in the vacuum-assisted group. Similar Apgar scores and NICU admissions were seen in both groups.

This data suggests vacuum-assistance is superior to forceps in operative vaginal deliveries, however neither of these studies were specific to deliveries in the OP position. A retrospective case study by Damron and Capeless [20] obtained data from 364 operative deliveries in the OP position. The authors found vacuum-assistance had a higher risk of primary instrument failure (33.1% vs. 13.6%, p < 0.0001), but a lower risk of anal sphincter injury (33.1% vs. 71.6%, p < 0.0001). The overall increase in the risk of anal sphincter injury with the use of forceps compared to vacuum has been shown in previous studies [21]. Interestingly this study showed the risk of anal sphincter injury was further increased in the OP position compared to OA (OR 3.25 vs OR 5.25). There was no evaluation of neonatal outcomes measured in this study. The authors’ exclusion of operative rotational procedures limited this study for the purposes of comparing the techniques.

Two further retrospective cohort studies examined the risk of anal sphincter injury in the OP vs. OA position with forceps-assisted or vacuum-assisted vaginal deliveries. Benavides and colleagues [22] showed that anal sphincter injury in forceps-assisted vaginal delivery was significantly more common in the OP position (51.5% vs. 32.9%, p = 0.003). In this study the absolute risk was shown to be lower than previously described [20]. The authors also excluded rotational forceps in the initial analysis, however a subsequent analysis showed that in 39 foetuses rotated from the OP to OA position with forceps, 31% resulted in anal sphincter injury, a rate comparable to the absolute risk for the OA position. A concurrent study examining vacuum-assisted vaginal deliveries also showed anal sphincter injury was more common in the OP position (41.7% vs 22.0%, p = 0.003) [23]. In comparison to the absolute risk shown previously [22], vacuum-assisted vaginal deliveries in the OP position appear to be associated with a reduced risk of anal sphincter injury. None of the above-mentioned studies were designed to show superiority, and further comparative studies would aid clinicians in deciding which instrument to choose.

Rotational operative delivery

Survey suggest that rotational forceps (RF) are being much less frequently used when when malposition delays delivery, attributed to a rise in use of rotational vacuum (RV) or caesarean section [24]. In a comparative retrospective study, women were eight times more likely to undergo caesarean section if RV was selected to assist birth rather than RF [25]. The low numbers in the RV group compared to RF in this study (107 vs. 1038) did not allow statistical comparison of maternal outcomes. Of the results obtained however, the absolute incidence of anal sphincter injury with RF remained low (2.4%), and no cases of anal sphincter injury were observed with the use of RV. The incidence of maternal haemorrhage was similar in both groups (1.8% RF vs. 1.9% RV). No significant differences were seen in neonatal outcomes such as lower 5-minute Apgar scores, admission to NICU, or cord blood acidosis, however there was a non-significant increase in shoulder dystocia in RF deliveries (6.2% vs. 3.7%). While this data suggests that RF is associated with the highest chance of achieving a vaginal birth without significant increase in maternal or neonatal morbidity, further studies are required for a definitive conclusion. Furthermore, delivery of the malpositioned foetus was either conducted or directly supervised by experienced obstetrician with at least 6-7 years of specialist training. This may have introduced bias as the skill level of the clinician may have impacted the outcomes of the chosen technique. This is further highlighted by the overall risk of anal sphincter injury being much lower than previous studies [20].

In a similar study, Stock and colleagues [26] also examined the maternal and neonatal outcomes of RF deliveries. This study was primarily designed for descriptive purposes and included a comparison with other types of deliveries in a secondary analysis. Thus, caution should be taken when interpreting this data. The initial analysis of 873 rotational forceps deliveries found a rate of anal sphincter injury of 6.1%. The secondary comparative analysis was limited by the inclusion of only successful RF deliveries in a single year (2008) and the lower number of cases in the RF group (n = 150). No comparison was made to RV, nor did the study include data on patients undergoing manual rotation prior to instrumental delivery. The rate of anal sphincter injury after RF delivery was 9.3% and comparable with non-rotational forceps (8.5%, p = 0.64), but higher than vacuum (1.9%, p = 0.005) or spontaneous delivery (2.9%, p < 0.001). No statistically significant differences in postpartum haemorrhage were observed between RF and non-rotational forceps (5.3% vs. 7.2%, p = 0.49) or ventouse delivery (5.3% vs. 2.5%, p = 0.25), however lower rates were observed for spontaneous delivery (5.3% vs. 2.3%, p = 0.027). It should be noted that the comparison groups are not specific for the OP position. There were no statistical differences in NICU admissions or neonatal encephalopathy between the modes of vaginal delivery. Interestingly, delivery by emergency caesarean showed an increase in NICU admission compared to RF (3.3% vs 11.2%, p = 0.002). Despite the limitations, this study showed RF deliveries overall had a low incidence of neonatal and maternal morbidity.

A recent meta-analysis compared the safety and efficacy of RF and RV [27]. Data was obtained for 5870 rotational vaginal deliveries performed with forceps. Most of this data came from retrospective cohort studies, with only one prospective study included. In direct comparison to RF, RV showed a significantly higher risk of failure in achieving vaginal delivery. There were no significant differences in maternal outcomes such as anal sphincter injury, haemorrhage, or extended tears. Furthermore, there was a significantly lower risk of neonatal trauma with RF, and no significant difference in NICU admission, neonatal jaundice, or shoulder dystocia. This study currently provides the most robust evidence in this area. However, it is important to note that no randomised controlled trials have been performed and the authors state the quality of included studies was generally poor with significant sources of bias such as moderate selection bias and a high risk of comparability and outcome assessment bias.

Manual rotation

Manual rotation (MR) of the foetal head from OP to OA position during the second stage of labour is a relatively simple intervention that may increase the chance of normal vaginal delivery. In one study, investigators showed that MR was a successful intervention in 90.3% of cases, with 69.6% successful on the first attempt [28]. Interestingly, none of the fourth or fifth attempts were successful, suggesting that more than three attempts may have no benefit. Rotation failure was more common in nulliparity and a maternal age >35 years. The authors showed the risk of anal sphincter injury was minimal in both successful and unsuccessful rotations, and that although manual rotation may induce foetal heart rate abnormalities, there is no association between foetal heart rate abnormalities after manual rotation and caesarean delivery.

Overall, this study suggests that MR may be an effective technique for reducing the caesarean delivery rate in patients with an OP position during labour. Although this opinion is shared by 97% of obstetricians in Australia and New Zealand, only a minority regularly perform MR [29]. Furthermore, it has been suggested that more obstetricians would be willing to perform the procedure if more robust evidence showed a reduction in the operative delivery rate [29].

Bahl and colleagues [30] conducted a prospective cohort study of 381 nulliparous women who had rotational operative vaginal deliveries, comparing MR with RV and RF. It is important to note that in this study, direct traction forceps followed MR. In this study MR was the most commonly performed method of rotation accounting for 42.8% of deliveries (followed by RF 38.1% and RV 19.1%). There were no significant differences in anal sphincter injury or postpartum haemorrhage between the three interventions. Additionally, there were no significant differences between the groups when comparing neonatal outcomes including 5-minute Apgar scores <7, cord blood acidosis, birth trauma, NICU admissions or shoulder dystocia. Compared with RV, MR was significantly less likely to result in sequential use of instruments (OR 0.01; 95% CI 0.002-0.09 p<0.05).  This data showed rotational operative vaginal deliveries including MR, RV and RF had a low failure rate (6.8%) and are associated with few adverse maternal and neonatal outcomes. This study was limited by its cohort design and low number of cases. Additionally, the authors presented no significance levels for their findings.

A recent systematic review investigating the efficacy of prophylactic MR to reduce operative delivery found only one small pilot study, which showed no clear difference in the operative delivery rate [31, 32]. Thus, there remains insufficient evidence to determine the efficacy of MR. However the POP-OUT study, a randomised controlled trial currently in progress, will determine the effect of MR at full dilatation in reducing the operative delivery rate, as well as a number of secondary maternal and neonatal outcomes [9]. The results of this trial may provide the robust evidence needed to inform future practice amongst obstetricians.

Recommendations

Based on the current available evidence, this review has demonstrated the following. Maternal posturing in the last four weeks of pregnancy or during labour has no benefit in reducing the incidence of OP position at or before delivery. Therefore, no posture should be imposed on women with OP position during labour. Rotational operative vaginal deliveries tend to have a low failure rate when performed by experienced clinicians, however may be associated with anal sphincter injury, despite the overall risk being low. Despite current trends favouring the use of rotational vacuum, the most current evidence supports the use of rotational forceps in achieving a successful vaginal delivery with no increase in maternal morbidity, and a lower rate of neonatal trauma. Manual rotation followed by direct traction forceps is a commonly performed method of delivery for the OP positioned foetus, however has only been directly compared to rotational forceps or vacuum in one study, with no demonstrable statistical difference in maternal or neonatal outcomes. At the completion of the POP-OUT study, new evidence may support an increasing role for manual rotation in the management of OP position at delivery.

Acknowledgements

The author would like to acknowledge Associate Professor Andrew Bisits from the Royal Hospital for Women for his mentorship and continuing passion for teaching medical students.

Conflicts of Interest

None declared.

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This review critically appraises the major considerations associated with oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) within the Australian context, and suggests implications for future research. Daily oral PrEP, tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) has demonstrated efficacy in preventing human immunodeficiency virus (HIV) transmission in MSM with an estimated risk reduction between 44.0 – 86.7% and even up to 99%, with consistent daily adherence. However, uptake has been slow, driven by high costs, limited availability, poor acceptance, and low concept awareness. Implementation of PrEP will rely heavily on primary care providers, who are at the forefront of health care services, in identifying high-risk patients, providing education, assessing readiness, and prescribing antiretroviral medication. Clinician scepticism and reluctance to prescribe PrEP can significantly impair access to this effective preventative strategy. Future research is essential to inform the best strategies in developing programs to support PrEP uptake, utilisation, and adherence in Australia. This will require collaboration and coordination between community health organisations, the health sector, and the general public. Open label and implementation research modelling real world effects, is urgently needed to respond to this gap in knowledge and is pivotal in driving the introduction of this effective primary prevention modality in Australia.

Background

Despite biotechnical and pharmaceutical advancements in primary, secondary, and tertiary prevention, human immunodeficiency virus (HIV) notifications have been on the rise in Australia since 1999 [1]. In Australia, 27,150 persons were living with HIV at the end of 2014 and 1,081 new cases are diagnosed annually, of which 80% are attributed to men who have sex with men (MSM) [1,2]. Furthermore, undiagnosed infections in MSM account for 31% of newly acquired HIV cases in Australia [3]. This urgently calls for original and unprecedented approaches in prevention and treatment to reduce the unrelenting high rates of infection.

A single pill taken daily has been shown to dramatically reduce HIV acquisition
A promising new strategy, combining both treatment and prevention, is pre-exposure prophylaxis (PrEP). A single pill taken daily, tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (200 mg/300 mg) has been shown to dramatically reduce HIV acquisition in uninfected, high-risk individuals [4-8]. TDF and FTC are nucleoside and nucleotide reverse transcriptase inhibitors and synergistically stop viral replication by interfering with viral DNA polymerase [2]. These agents have classically been used to treat HIV infection and are now recommended as pre-exposure prophylaxis. Several trials have indicated that PrEP is safe and effective in preventing HIV amongst MSM [4,5], serodiscordant couples [6], and injecting drug users [8]. This prompted the United States Center for Disease Control and Prevention (CDC) to recommend immediate utilisation in 2012 [9]. Although PrEP was recently approved by the Therapeutic Goods Administration (May 2016), this costly drug is yet to be funded through the Australian Pharmaceutical Benefits Scheme (PBS).

This paper focuses on critically appraising the significant considerations associated with introducing oral PrEP in the Australian MSM population, and suggests implications for future research. This review discusses the efficacy of HIV chemoprophylaxis, evaluates current awareness, accessibility and acceptance of PrEP in Australia, and finally, examines the considerations for future drug implementation within the Australian context.

Establishing efficacy of oral HIV pre-exposure chemoprophylaxis

Clinical trials investigating PrEP efficacy and safety in MSM

Research investigating the efficacy of HIV chemoprophylaxis in MSM commenced in 2005 and evidence of success was first demonstrated in the Gates Foundation-funded Phase III multinational Preexposure Prophylaxis Initiative (iPrEx) study (Table 1) [4]. Daily oral TDF/FTC was evaluated in 2499 MSM participants from the United States, South America, Thailand, and Africa [4]. Subjects were randomised into either a placebo or a daily oral TDF/FTC cohort [4]. Follow up was conducted every 4 weeks and included provision of study medications, compliance counselling, and comprehensive prevention services. In total, adjusting for modified intention-to-treat, there was a higher seroconversion rate in the placebo arm (64/1248 subjects) compared to the TDF/FTC arm (36/1251 subjects), corresponding with an overall relative reduction in HIV risk by 44% (95% confidence interval [CI] 15-63%; p = 0.005) [4]. Adherence across participants was 50% based on pill counting and self-reported data, and estimated at 51% based on plasma detection of tenofovir [4].  Longer follow up did not reveal improvements in antiretroviral efficacy (p = 0.44). Of importance, the independent contribution of access to standard preventative services (HIV/STI testing, provision of condoms, risk reduction counselling, etc.) in the final outcome analysis is unknown. However, it is likely to have contributed positively to efficacy rates.

Table 1: Major studies on oral pre-exposure prophylaxis.

The open-label trial sponsored by the UK Medical Research Council, Pre-exposure Prophylaxis to Prevent the Acquisition of HIV-1 Infection (PROUD) study, evaluated the efficacy of TDF/FTC (245 mg/ 200 mg) in 544 HIV negative MSM reporting recent high-risk sexual activity (receptive anal intercourse without a condom) [5]. Subjects recruited from 13 British sexual health clinics were randomised into two cohorts – an immediate group, which received daily oral TDF/FTC at the time of enrolment, or into a deferred group, receiving the study medication one year later [5]. High levels of post-exposure prophylaxis (PEP) was utilised in both the deferred (n = 85) and immediate (n = 12) groups, acting as a confounding variable, thus altering final outcomes [5]. Despite this, rates of HIV were lower in the immediate group, 3/243 person-years of follow up (1.2 cases per 100 person-years) (90% CI 0.4-2.9) compared to the deferred group, 20/222 person-years (9.0 per 100 person-years) (90% CI 6.1-12.8; p = 0.0001) producing an 86.7% (90% CI 64–96%; p = 0.0001) relative risk reduction [5]. The demonstrated efficacy of PrEP was higher in this trial, compared to the iPrEx study. PROUD participants knew they were taking PrEP whereas iPrEx subjects were blinded to their treatment groups. This open label design gave participants the knowledge that they were taking PrEP that would prevent HIV, thereby improving motivation to adhere to study medication and generating overall better efficacy rates. Further non-blinded research should be conducted within the context of a real life, implementation based framework. Non-blinded study design can improve access of non-subsidized TDF/FTC to at-risk populations and heighten participant confidence and motivation while taking study medication.

Clinical trials investigating PrEP efficacy and safety in heterosexual couples and women

Two other trials reproduced similar results in serodiscordant heterosexual couples (Table 1). The Partners PrEP study indicated a 75% (95% CI 55–87%; p < 0.001) risk reduction with daily oral TDF/FTC in Kenyan and Ugandan serodiscordant couples [6].  The TDF 2 trial investigated TDF/FTC in 1219 high-risk heterosexual men and women in Botswana and demonstrated an overall 62.2% (95% CI 21.5-83.4%; p = 0.03) reduction in HIV acquisition compared to placebo [7].

In contrast, the FEM PrEP (Pre-exposure Prophylaxis Trial for HIV Prevention among African Women) and VOICE (Vaginal and Oral Interventions to Control the Epidemic) trials did not observe any therapeutic benefit with TDF/FTC in uninfected, high-risk women (Table 1) [10,11]. In addition to investigating oral TDF/FTC, the VOICE study also evaluated oral TDF alone and tenofovir (TFV) as an antiretroviral vaginal gel [11]. Research arms in both studies were prematurely terminated following a rise in HIV infections and due to a lack of evidence to support efficacy of oral [10,11] and vaginal preparations [11]. The vastly differing outcomes between these studies and previous studies are currently the focus of investigation.

Factors influencing PrEP efficacy

Adherence and quality of drug protection

The varying rates of PrEP efficacy across the aforementioned studies can be attributed to suboptimal medication adherence rates [4-11]. Adherence was measured by pill counting and participant self-reporting. Both methods are unreliable indicators, given the potential for misreporting and the assumption that subjects had actually taken the number of pills counted [4,6,7,10,11]. Pharmacokinetic measurements of plasma tenofovir in seronegative subjects are more reliable [12].

In the iPrEx study, overall reduction in HIV risk was 44%, with a higher rate of protection of 92% (95% CI 1.7 -99.3; p < 0.001) in those with detectable plasma tenofovir levels compared to those with undetectable plasma drug levels [4].

A quantitative study analysed the impact of varying doses against antiretroviral efficacy, based on plasma tenofovir data obtained from an iPrEx substudy and a separate trial involving monitored oral TDF dosing [12]. This study found a 99% (95% CI 96 to > 99%; p = 0.016) risk reduction when PrEP was taken 7 days a week [12]. Adherence based on detectable levels of plasma tenofovir was suggested to be a key predictor of TDF/FTC efficacy in HIV prevention [4-7,12]. However, cautious interpretation of plasma drug concentrations as a sole measure of adherence should be maintained. Factors that could alter plasma levels include individual pharmacokinetic variability, pharmacogenetic responses, dosing regimens, and co-administration of other drugs [13].

Perhaps of greater clinical importance is to appreciate the factors associated with low adherence rates. In a qualitative New York study, MSM participants rated concerns about short- and long-term side effects of chronic PrEP exposure as the greatest barrier to PrEP adherence [15]. Across clinical trials, no serious events were documented, however, long-term consequences are unknown [4,5]. Self-limiting and short-term side effects, including mild nausea and headaches, were reported [4,5] along with mild elevations in serum alanine aminotransferase [10] and serum creatinine [10,11]. Future educational programs should directly address these concerns by presenting the available evidence to suitable candidates to support their informed decision to take PrEP.

Comparatively, research participants in the VOICE trial based in South Africa, Uganda, and Zimbabwe emphasised poor cultural and social acceptance as reasons underpinning poor adherence [14]. Specifically, these barriers were the cultural stigmata of being perceived as HIV positive, fear of scrutiny, and lack of partner support [14]. Furthermore, there was a prevailing view among research participants (70%) of being at low risk for HIV acquisition, which could have undermined the motivation to take the study’s drugs [10]. In Africa, cultural, societal, and perceptual influences appeared to be the strongest barriers to adherence, while North American attitudinal studies suggested primary concerns revolved around health consequences and medication safety. Meanwhile, future research should investigate the unique Australian factors that would predispose to poor adherence, as this information is lacking in the literature.

Access to preventative health services

Adherence alone cannot fully explain the substantial variability observed in drug efficacy rates. Experimental design in these trials included comprehensive HIV/STI prevention services [4,6,7]. The exact impact of these services in contributing to medication efficacy in the final analysis is unknown, however, prevention services alongside PrEP are likely to be important for reducing HIV infection.

Although PrEP has been demonstrated to be an effective tool in HIV prevention, use of this drug is complicated by concerns over increased risky sexual behaviour and higher rates of sexually transmitted infections [15]. There is conflicting data outside of clinical trials concerning risk compensation, emphasising a need for open label implementation research to better inform these associations in Australia. Meanwhile, applications of PrEP within the Australian context should involve a synergistic, multimodal approach, which includes expansion of prevention services providing intense and frequent HIV/STI testing, behavioural counselling, and provision of condoms [16-19].

Current status of PrEP in Australia

Outcomes from the aforementioned clinical trials will shape the future landscape of HIV prevention in Australia. These studies establish PrEP as an effective tool in preventing HIV transmission in MSM [4,5]. The current status of PrEP in Australia and the likelihood of successful implementation will be led by discussion of three key factors – awareness, accessibility, and acceptance.

Awareness

Advocacy organisations, HIV foundations, and research groups have recently made strong messages supporting PrEP utilisation in Australia. These messages seem to have garnered considerable awareness of PrEP, evidenced by a 2015 Australian study reporting 76.2% of homosexual and bisexual respondents had previously heard of PrEP [20]. Despite these efforts, few Australian MSM, 38/1251 (3.0%), have ever used PrEP, [20] with utilisation more likely to be associated with high-risk sexual practices (unprotected anal sex with casual partners rather than with regular partners) (adjusted odds ratio [AOR]  2.36, 95% CI 1.24-4.48; p < 0.10) [21]. Public health campaigns targeted at high-risk populations at sexual health clinics, at social venues, and through gay community media should continue raising awareness with the goal of improving PrEP uptake. Despite high levels of awareness, the actual utilisation of PrEP in Australia is complicated by several factors that are subsequently discussed.

There is considerable awareness of PrEP utilisation in Australia; however, funding remains unavailable

Accessibility

Oral TDF/FTC was recently approved for the indication of pre-exposure prophylaxis in Australia.  However, funding to subsidise this medication remains unavailable through the Australian PBS. TDF/FTC can be acquired through participation in clinical trials, from overseas vendors at a cost of AU$1,300/year, as a prescription costing AU$13,500/year or obtained from another person prescribed TDF/FTC for HIV infection [22]. Undoubtedly, improved uptake of PrEP will require financial subsidisation and support through the PBS. From a population viewpoint, PrEP is expensive and extending coverage to all MSM would not be cost effective in the Australian context [23]. However, one study suggested PrEP would be cost effective if one dose cost less than $15/day and had > 75% efficacy rate [24]. Conflicting research demands further investigation to ascertain the specific groups best suited for this drug, taking into consideration the individual biopsychosocial benefits and cost to society.

Acceptance and attitudes

Willingness to take PrEP among uninfected or sero-status unknown Australian MSM fell from 327/1161 (28.2%) in 2011 to 285/1223 (23.3%) in 2013 (AOR = 0.83, 95% CI 0.68-1.00, p = 0.05) [25]. Another Australian study suggested that less than half of MSM (43.2%) were willing to participate in research trials evaluating antiretroviral prophylaxis [26]. These studies demonstrate negative attitudes and lack of acceptance towards PrEP. Encouragingly, however, very high-risk MSM in serodiscordant partnerships were more interested in PrEP (AOR = 3.23, 95% CI 1.48-7.05, p = 0.003), representing a group likely to derive the greatest benefit from this drug [25]. Future Australian research should be conducted to inform of the best strategies aimed at improving understanding and developing greater acceptance of PrEP amongst other MSM groups with hesitations towards antiretroviral prevention.

Future agenda for PrEP in Australia

Clinician aspects

Primary care clinics are often the first point of health care contact for many consumers in Australia, including MSM who would be suitable candidates for PrEP. A survey of 1175 physicians in the US and Canada revealed that only 9% had ever prescribed PrEP and 26% were unsure or would not prescribe PrEP to high-risk persons [27]. Multiple studies analysing physician attitudes towards PrEP describe concerns regarding real world effectiveness, non-adherence, drug resistance, toxicity, and risk compensation as reasons against PrEP [25,28-30].

Drug resistance is rare, however, can develop when PrEP is taken in acute seronegative HIV infection [31]. Management of drug resistance is challenging given that exclusion of acute infection is practically difficult in persons engaging in frequent sexual activity and delaying treatment can increase the risk of HIV infection. Close monitoring and intensive HIV surveillance after initiation of PrEP is vital in minimising the risk of HIV drug resistance [31].

Risk compensation associated with PrEP is another concern amongst clinicians. Behavioural disinhibition and risky sexual practices can increase STI incidence [32,33]. Early detection and management of STIs through frequent and routine screening every three months can reduce transmission and reduce infection incidence [32,33]. Longitudinal and real world data analysing drug resistance and risk compensation are limited. Further inquiry is needed to inform the safest and most effective therapeutic application of PrEP within the Australian context.

The surmounting evidence supporting PrEP in MSM is compelling and with recent approval in Australia, there has been general acceptance of this effective measure across public sexual health centres and general practice clinics. Future frameworks should embody programs supporting physician awareness of PrEP, improving comfort in discussing sexual health topics, assessing HIV risk, prescribing TDF/FTC, supporting frequent screening for STIs, managing adherence, and monitoring for resistance and toxicity (Figure 1). Primary care providers will be instrumental in improving the delivery of PrEP and monitoring for drug safety as PrEP becomes more available in Australia.

Figure 1: Factors influencing successful implementation of PrEP in Australia

Facilitating PrEP in Australia

In order to implement PrEP in Australia, facilitators for uptake and adherence will need to be considered. Respondents in US studies have named affordability of PrEP, availability of free HIV testing centres, accessibility to sexual health services, individualised counselling programs to assist with antiretroviral therapy, and a coherent understanding of what pre-exposure prophylaxis entails, as important factors facilitating uptake [15,34]. Future Australian policy development will need to account for these same issues to maximise PrEP impact.

This can only be achieved with more research to fill a major gap in the current understanding of PrEP in Australia. Future research could run as an Australian nationwide, implementation-based, open label study and assess the impact of TDF/FTC in high-risk MSM with three-monthly consultations. Outcomes would ideally inform on real world effectiveness, adherence, long-term safety considerations, risk compensation and issues surrounding utilisation. Successful PrEP rollout in Australia will require a systematic, multi-sectoral approach involving clinician training, expansion of preventative services, support from community health organisations, and increased community engagement (Figure 1). These partnerships will improve understanding, broaden acceptance, and maximise the positive impacts of PrEP in Australia.

Conclusion

This review aimed to evaluate the factors influencing PrEP implementation in Australia and to suggest an immediate research agenda. Implementation trials would bridge the gap between clinical studies and real world application through examination of PrEP within the Australian environment. Outcome variables would address adherence, awareness, accessibility, acceptance, clinician factors, cost/benefit analysis, patient motivations, and patient experiences with PrEP. Analysis of these findings will produce strategies to improve delivery of services, programs, and policies. In doing so, we optimise the successful impact of PrEP in a new primary prevention model and work towards a stronger and healthier future.

Acknowledgements

None.

Conflicts of Interest

None declared.

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